Citizendia

Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl MembraneA biological membrane or biomembrane is an enclosing or separating Amphipathic layer that acts as a barrier within or around a cell. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. An Integral Membrane Protein ( IMP) is a Protein Molecule (or assembly of proteins that is permanently attached to the Biological membrane. A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living Transmembrane receptors are Integral membrane proteins which reside and operate typically within a cell's Plasma membrane, but also in the membranes of In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Protein purification is a series of processes intended to isolate a single type of Protein from a complex mixture Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins. Glycosylphosphatidylinositol ( GPI anchor) is a Glycolipid that can be attached to the C-terminus of a Protein during Posttranslational An Integral Membrane Protein ( IMP) is a Protein Molecule (or assembly of proteins that is permanently attached to the Biological membrane.

The reversible attachment of proteins to biological membranes has shown to regulate cell signaling and many other important cellular events, through a variety of mechanisms. Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions [1] For example, the close association between many enzymes and biological membranes may bring them into close proximity with their lipid substrate(s). Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins [2] Membrane binding may also promote rearrangement, dissociation, or conformational changes within many protein structural domains, resulting in an activation of their biological activity. A macromolecule is usually flexible and dynamic It can change its shape in response to changes in its environment or other factors each possible shape is called a conformation and a transition [3][4] Additionally, the positioning of many proteins are localized to either the inner or outer surfaces or leaflets of their resident membrane. [5] This facilitates the assembly of multi-protein complexes by increasing the probability of any appropriate protein-protein interactions.

Schematic representation of the different types of interaction between monotopic membrane proteins and the cell membrane: 1. interaction by an amphipathic α-helix parallel to the membrane plane (in-plane membrane helix) 2. interaction by a hydrophic loop 3. interaction by a covalently bound membrane lipid (lipidation) 4. electrostatic or ionic interactions with membrane lipids (e.g. through a calcium ion)
Schematic representation of the different types of interaction between monotopic membrane proteins and the cell membrane: 1. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer interaction by an amphipathic α-helix parallel to the membrane plane (in-plane membrane helix) 2. A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which interaction by a hydrophic loop 3. interaction by a covalently bound membrane lipid (lipidation) 4. electrostatic or ionic interactions with membrane lipids (e. In Physics, Chemistry, and Biology, intermolecular forces are forces that act between stable Molecules or between functional groups of g. through a calcium ion)

Contents

Binding of peripheral proteins to the lipid bilayer

PH domain of phospholipase C delta 1. Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (intracellular side). Layer of lipid phosphates - yellow dots.
PH domain of phospholipase C delta 1. Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (intracellular side). Layer of lipid phosphates - yellow dots.

Peripheral membrane proteins may interact with other proteins or directly with the lipid bilayer. A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. In the latter case, they are then known as amphitropic proteins. [3] Some proteins, such as G-proteins and certain protein kinases, interact with transmembrane proteins and the lipid bilayer simultaneously. GTP chemical structurepng|thumb|180px| Guanosine triphosphate]] G proteins short for guanine nucleotide-binding proteins, are a family of Proteins involved A protein kinase is a Kinase Enzyme that modifies other Proteins by chemically adding Phosphate groups to them ( Phosphorylation) Some polypeptide hormones, antimicrobial peptides, and neurotoxins accumulate at the membrane surface prior to locating and interacting with their cell surface receptor targets, which may themselves be peripheral membrane proteins. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Antimicrobial peptides (also called host defence peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels

The Phospholipid bilayer that forms the cell surface membrane consists of a hydrophobic inner core region sandwiched between two regions of hydrophilicity, one at the inner surface and one at the outer surface of the cell membrane (see lipid bilayer article for a more detailed structural description of the cell membrane). A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. In Chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro- and for fear phobos) refers to the physical property of Hydrophile, from the Greek (hydros "water" and φιλια (philia "friendship" refers to a physical property of a Molecule A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. The inner and outer surfaces, or interfacial regions, of model phospholipid bilayers have been shown to have a thickness of around 8 to 10 Å, although this may be wider in biological membranes that include large amounts of gangliosides or lipopolysaccharides. Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate An ångström or angstrom (symbol Å) (ˈɔːŋstrəm Swedish: ˈɔ̀ŋstrœm is an internationally recognized non- SI unit of length equal MembraneA biological membrane or biomembrane is an enclosing or separating Amphipathic layer that acts as a barrier within or around a cell. Ganglioside is a compound composed of a Glycosphingolipid ( Ceramide and Oligosaccharide) with one or more Sialic acids (AKA N-acetylneuraminic Lipopolysaccharides ( LPS) are large Molecules consisting of a Lipid and a Polysaccharide joined by a Covalent bond; they are found [6] The hydrophobic inner core region of typical biological membranes may have a thickness of around 27 to 32 Å, as estimated by Small angle X-ray scattering (SAXS). MembraneA biological membrane or biomembrane is an enclosing or separating Amphipathic layer that acts as a barrier within or around a cell. Small-angle X-ray scattering (SAXS is a Small-angle scattering (SAS technique where the elastic scattering of X-rays (wavelength 0 [7] The boundary region between the hydrophobic inner core and the hydrophilic interfacial regions is very narrow, at around 3Å, (see lipid bilayer article for a description of its component chemical groups). A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. Moving outwards away from the hydrophobic core region and into the interfacial hydrophilic region, the effective concentration of water rapidly changes across this boundary layer, from nearly zero to a concentration of around 2M. In Chemistry, concentration is the measure of how much of a given substance there is mixed with another substance [8][9] The phosphate groups within phospholipid bilayers are fully hydrated or saturated with water and are situated around 5 Å outside the boundary of the hydrophobic core region (see Figures ). [10]

Some water-soluble proteins associate with lipid bilayers irreversibly and can form transmembrane alpha-helical or beta-barrel channels. A beta barrel is a large Beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last Such transformations occur in pore forming toxins such as colicin A, alpha-hemolysin, and others. Pore forming toxins (PFTs are Protein Toxins, typically (but not exclusively produced by Bacteria, such as ''C A colicin is a type of Bacteriocin produced by and toxic to some strains of Escherichia coli. They may also occur in BcL-2 like proteins which has been shown to play a role in cellular apoptosis , in some amphiphilic antimicrobial peptides , and in certain annexins . Antimicrobial peptides (also called host defence peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life Annexin is a common name for a group of cellular Proteins The annexins are a family of proteins first described in the 1980s that bind Phospholipid membrane These proteins are usually described as peripheral as one of their conformational states is water-soluble or only loosely associated with a membrane. [11]

Membrane binding mechanisms

Bee venom phospholipase A2 (1poc). Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - red dots (extracellular side). Layer of lipid phosphates - yellow dots.
Bee venom phospholipase A2 (1poc). Phospholipases A2 (PLA2s are upstream regulators of many inflammatory processes Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - red dots (extracellular side). Layer of lipid phosphates - yellow dots.

The association of a protein with a lipid bilayer may involve significant changes within tertiary structure of a protein. A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. In Biochemistry and Chemistry, the tertiary structure of a Protein or any other Macromolecule is its three-dimensional structure as defined These may include the folding of regions of protein structure that were previously unfolded or a re-arrangement in the folding or a refolding of the membrane-associated part of the proteins . Protein folding is the physical process by which a Polypeptide folds into its characteristic and functional three-dimensional structure. It also may involve the formation or dissociation of protein quaternary structures or oligomeric complexes, and specific binding of ions, ligands, or regulatory lipids. In Biochemistry, quaternary structure is the arrangement of multiple folded Protein molecules in a multi-subunit complex In Chemistry, an oligomer consists of a limited number of Monomer units (ολιγος or oligos is Greek for "a few" in contrast to a An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge In Biochemistry, a ligand ( latin ligare = to bind is a substance that is able to bind to and form a complex with a Biomolecule Phosphatidylinositol (abbreviated PtdIns or PI is a minor Phospholipid component in the cytosolic side of eukaryotic Cell membranes.

Typical amphitropic proteins must interact strongly with the lipid bilayer in order to perform their biological functions. These include the enzymatic processing of lipids and other hydrophobic substances, membrane anchoring, and the binding and transfer of small nonpolar compounds between different cellular membranes. These proteins may be anchored to the bilayer as a result of hydrophobic interactions between the bilayer and exposed nonpolar residues at the suface of a protein, by specific non-covalent binding interactions with regulatory lipids , or through their attachment to covalently-bound lipid anchors. In lipid anchored proteins, a covalently attached Fatty acid such as Palmitate or Myristate serves to anchor them to either face of the Cell membrane

It has been shown that the membrane binding affinities of many peripheral proteins depend on the specific lipid composition of the membrane with which they are associated. [12]

Non-specific hydrophobic association

Amphitropic proteins associate with lipid bilayers via various hydrophobic anchor structures. In Chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro- and for fear phobos) refers to the physical property of Such as amphiphilic α-helixes, exposed nonpolar loops, post-translationally acylated or lipidated amino acid residues, or acyl chains of specifically bound regulatory lipids such as phosphatidylinositol phosphates. Amphiphile (from the Greek αμφις amphis both and φιλíα Philia: love friendship is a term describing a Chemical compound possessing both A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which Phosphatidylinositol (abbreviated PtdIns or PI is a minor Phospholipid component in the cytosolic side of eukaryotic Cell membranes. Hydrophobic interactions have been shown to be important even for highly cationic peptides and proteins, such as the polybasic domain of the MARCKS protein or histactophilin, when their natural hydrophobic anchors are present. MARCKS proteins (myristoylated alanine-rich C-kinase substrate play important roles in cell shape Cell motility, Secretion, Transmembrane transport, and [13]

Covalently bound lipid anchors

Lipid anchored proteins are covalently attached to different fatty acid acyl chains on the cytoplasmic side of the cell membrane via palmitoylation, myristoylation, or prenylation. In lipid anchored proteins, a covalently attached Fatty acid such as Palmitate or Myristate serves to anchor them to either face of the Cell membrane In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which acyl group ( IUPAC name alkanoyl) is a Functional group derived by the removal of one or more Hydroxyl group from an Oxoacid. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer S-Palmitoylation is the covalent attachment of fatty acids such as Palmitic acid, to Cysteine residues of membrane proteins Myristoylation is an irreversible co-translational (during translation Protein modification found in Animals Plants Fungi and Viruses Prenylation or isoprenylation or lipidation is the addition of Hydrophobic molecules to a Protein. At the cell surface, on the opposite side of the cell membrane lipid anchored proteins are covalently attached to the lipids glycosylphosphatidylinositol (GPI) and cholesterol. In lipid anchored proteins, a covalently attached Fatty acid such as Palmitate or Myristate serves to anchor them to either face of the Cell membrane Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Glycosylphosphatidylinositol ( GPI anchor) is a Glycolipid that can be attached to the C-terminus of a Protein during Posttranslational Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian [14][15] Protein association with membranes through the use of acylated residues is a reversible process, as the acyl chain can be buried in a protein's hydrophobic binding pocket after dissociation from the membrane. acyl group ( IUPAC name alkanoyl) is a Functional group derived by the removal of one or more Hydroxyl group from an Oxoacid. For articles on other forms of reversibility including reversibility of microscopic dynamics see Reversibility (disambiguation. This process occurs within the beta-subunits of G-proteins . GTP chemical structurepng|thumb|180px| Guanosine triphosphate]] G proteins short for guanine nucleotide-binding proteins, are a family of Proteins involved Perhaps because of this additional need for structural flexibility, lipid anchors are usually bound to the highly flexible segments of proteins tertiary structure that are not well resolved by protein crystalographic studies. X-ray crystallography is a method of determining the arrangement of Atoms within a Crystal, in which a beam of X-rays strikes a crystal and scatters

Specific protein-lipid binding

P40phox PX domain of NADPH oxidase Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (intracellular side). Layer of lipid phosphates - yellow dots.
P40phox PX domain of NADPH oxidase Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (intracellular side). Layer of lipid phosphates - yellow dots.

Some cytosolic proteins are recruited to different cellular membranes by recognizing certain types of lipid found within a given membrane. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. [16] Binding of a protein to a specific lipid occurs via specific membrane-targeting structural domains that occur within the protein and have specific binding pockets for the lipid head groups of the lipids to which they bind. Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate This is a typical biochemical protein-ligand interaction, and is stabilized by the formation of intermolecular hydrogen bonds, van der Waals interactions, and hydrophobic interactions between the protein and lipid ligand. Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as In Biochemistry, a ligand ( latin ligare = to bind is a substance that is able to bind to and form a complex with a Biomolecule A hydrogen bond results from a Dipole-dipole force between an Electronegative atom and a Hydrogen atom bonded to Nitrogen, Oxygen The Van der Waals equation is an Equation of state that can be derived from a special form of the potential between a pair of molecules (hard-sphere repulsion In Chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro- and for fear phobos) refers to the physical property of In Chemistry, a ligand is either an Atom, Ion, or Molecule (see also Functional group) that bonds to a central metal generally Such complexes are also stabilized by the formation of ionic bridges between the aspartate or glutamate residues of the protein and lipid phosphates via interveening calcium ions (Ca2+). Aspartic acid (abbreviated as Asp or D; Asx or B represent either aspartic acid or Asparagine) is an α- Amino acid Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Such ionic bridges can occur and are stable when ions (such as Ca2+) are already bound to a protein in solution, prior to lipid binding. The formation of ionic bridges is seen in the protein-lipid interaction between both protein C2 type domains and annexins. A C2 domain is a Protein Structural domain involved in targeting proteins to Cell membranes. Annexin is a common name for a group of cellular Proteins The annexins are a family of proteins first described in the 1980s that bind Phospholipid membrane

Protein-lipid electrostatic interactions

Any positively charged protein will be attracted to a negatively charged membrane by nonspecific electrostatic interactions. Electrostatics is the branch of Science that deals with the Phenomena arising from what seems to be stationary Electric charges Since Classical However, not all peripheral peptides and proteins are cationic, and only certain sides of membrane are negatively charged. MembraneA biological membrane or biomembrane is an enclosing or separating Amphipathic layer that acts as a barrier within or around a cell. These include the cytoplasmic side of plasma membranes, the outer leaflet of outer bacterial membranes and mitochondrial membranes. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Therefore, electrostatic interactions play an important role in membrane targeting of electron carriers such as cytochrome c, cationic toxins such as charybdotoxin, and specific membrane-targeting domains such as some PH domains, C1 domains, and C2 domains. Electrostatics is the branch of Science that deals with the Phenomena arising from what seems to be stationary Electric charges Since Classical This article deals with protein targeting in Eukaryotes except where noted The electron is a fundamental Subatomic particle that was identified and assigned the negative charge in 1897 by J Cytochrome c, or cyt c (horse heart PDB 1HRC is a small Heme Protein found loosely associated with the inner membrane Charybdotoxin (CTX is a 37 Amino acid Neurotoxin from the venom of the Scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated Pleckstrin homology domain (PH domain is a Protein domain of approximately 120 Amino acids that occurs in a wide range of proteins involved in intracellular signaling C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG as well as the analogous A C2 domain is a Protein Structural domain involved in targeting proteins to Cell membranes.

Electrostatic interactions are strongly dependent on the ionic strength of the solution. The ionic strength, I, of a solution is a function of the Concentration of all Ions present in a Solution. These interactions are relatively weak at the physiological ionic strength (0.14M NaCl): ~3 to 4 kcal/mol for small cationic proteins, such as cytochrome c, charybdotoxin or hisactophilin. A molar Solution is one that contains one mole of solute per Litre of solution Cytochrome c, or cyt c (horse heart PDB 1HRC is a small Heme Protein found loosely associated with the inner membrane Charybdotoxin (CTX is a 37 Amino acid Neurotoxin from the venom of the Scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated [17][18][13]

Spatial position in membrane

Orientations and penetration depths of many amphitropic proteins and peptides in membranes are studied using site-directed spin labeling,[19] chemical labeling, measurement of membrane binding affinities of protein mutants,[20] fluorescence spectroscopy,[21] solution or solid-state NMR spectroscopy,[22] ATR FTIR spectroscopy,[23] X-ray or neutron diffraction,[24] and computational methods. Site-directed spin labeling is a technique for investigating Protein local dynamics using Electron spin resonance. A process by which the genetic information of an Organism is changed in a stable manner either in nature or experimentally by the use of Chemicals or Radiation. Fluorescence is a Luminescence that is mostly found as an Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is the name given to a technique which exploits the magnetic properties of certain nuclei Fourier transform spectroscopy is a measurement technique whereby spectra are collected based on measurements of the temporal coherence of a radiative source [25][26][27][28]

Two distinct membrane-association modes of proteins have been identified. Typical water-soluble proteins have no exposed nonpolar residues or any other hydrophobic anchors. Therefore, they remain completely in aqueous solution and do not penetrate into the lipid bilayer, which would be energetically costly. Such proteins interact with bilayers only electrostatically, for example, ribonuclease and poly-lysine interact with membranes in this mode. Ribonuclease, abbreviated commonly as RNase, is a Nuclease that catalyzes the degradation of RNA into smaller components Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2 However, typical amphitropic proteins have various hydrophobic anchors that penetrate the interfacial region and reach the hydrocarbon interior of the membrane. Such proteins "deform" the lipid bilayer, decreasing the temperature of lipid fluid-gel transition. [29] The binding is usually a strongly exothermic reaction. [30] Association of amphiphilic α-helices with membranes occurs similarly. [31][24] Intrinsically unstructured or unfolded peptides with nonpolar residues or lipid anchors can also penetrate the interfacial region of the membrane and reach the hydrocarbon core, especially when such peptides are cationic and interact with negatively charged membranes. Intrinsically unstructured proteins, often referred to as naturally unfolded proteins or disordered proteins, are Proteins characterized by their lack of Denaturation is a process in which Proteins or Nucleic acids lose their structure (tertiary structure by application of some external stress or compound for [32][33][34]

Categories of peripheral proteins

Enzymes

Peripheral enzymes participate in metabolism of different membrane components, such as lipids (phospholipases and cholesterol oxidases), cell wall oligosaccharides (glycosyltransferase and transglycosidases), or proteins (signal peptidase and palmitoyl protein thioesterases). Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble A cell wall is a tough flexible and sometimes fairly rigid layer surrounding a cell, located external to the Cell membrane, which provides the cell with structural An oligosaccharide is a Saccharide polymer containing a small number (typically three to ten of component sugars also known as Simple sugars. Lipases can also digest lipids that form micelles or nonpolar droplets in water. A lipase is a Water-soluble Enzyme that Catalyzes the Hydrolysis of Ester bonds in water–insoluble Lipid A micelle (rarely micella, plural micelles) is an aggregate of Surfactant molecules dispersed in a liquid Colloid.

ClassFunctionPhysiologyStructure
Alpha/beta hydrolase foldCatalyzes the hydrolysis of chemical bonds. The alpha/beta hydrolase fold is common to a number of Hydrolytic enzymes of widely differing phylogenetic origin and catalytic function Hydrolysis is a Chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions which may go on to participate in further reactions [35]Includes bacterial, fungal, gastric and pancreatic lipases, palmitoyl protein thioesterases, cutinase, and cholinesterases[1]
Phospholipase A2 (secretory and cytosolic)Hydrolysis of sn-2 fatty acid bond of phospholipids. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ A lipase is a Water-soluble Enzyme that Catalyzes the Hydrolysis of Ester bonds in water–insoluble Lipid Thioesterases are enzymes which belong to the Esterase family Cutin is one of two Waxy polymers that are the main components of the Plant cuticle which covers all aerial surfaces of Plants The other major cuticle polymer In Biochemistry, cholinesterase is an enzyme that catalyzes the Hydrolysis of the Neurotransmitter Acetylcholine into Phospholipases A2 (PLA2s are upstream regulators of many inflammatory processes In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate [36]Lipid digestion, membrane disruption, and lipid signaling. Lipid signaling broadly defined refers to any biological signaling event involving a Lipid messenger that binds and activates a receptor. [2] [3]
Phospholipase CHydrolyzes PIP2, a phosphatidylinositol, into two second messagers, inositol triphosphate and diacylglycerol. Phospholipase C is a class of Enzymes that cleave Phospholipids just before the Phosphate group (see Figure Phosphatidylinositol (abbreviated PtdIns or PI is a minor Phospholipid component in the cytosolic side of eukaryotic Cell membranes. Inositol trisphosphate or inositol 145-trisphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3 A diglyceride, or a diacylglycerol (DAG is a Glyceride consisting of two Fatty acid chains covalently bonded to a Glycerol [37]Lipid signaling[4]
Cholesterol oxidasesOxidizes and isomerizes cholesterol to cholest-4-en-3-one. Lipid signaling broadly defined refers to any biological signaling event involving a Lipid messenger that binds and activates a receptor. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian [38]Depletes cellular membranes of cholesterol, used in bacterial pathogenesis. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The term pathogenesis means step by step development of a disease due to a series of changes in the structure and /or function of a cell/tissue/organ being caused by a microbial, chemical or physical [5]
Carotenoid oxygenaseCleaves carotenoids. Carotenoid oxygenases are a family of Enzymes involved in the Cleavage of Carotenoids to produce for example Retinol, commonly Carotenoids are organic Pigments that are naturally occurring in Chromoplasts of plants and some other photosynthetic Organisms [39]Carotenoids function in both plants and animals as hormones (includes vitamin A in humans), pigments, flavors, floral scents and defense compounds. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Vitamin A refers to a family of similarly shaped molecules the Retinoids. For the drug referred to as "pigment" see Black tar heroin. Flavor or flavour is the sensory impression of a Food or other substance, and is determined [6]
LipoxygenasesIron-containing enzymes that catalyze the dioxygenation of polyunsaturated fatty acids. Lipoxygenases ( are a family of Iron -containing Enzymes that catalyse the Dioxygenation of Polyunsaturated Fatty acids in Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst Lipoxygenases ( are a family of Iron -containing Enzymes that catalyse the Dioxygenation of Polyunsaturated Fatty acids in In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which [40]In animals lipoxygenases are involved in the synthesis of inflammatory mediators known as leukotrienes. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Leukotrienes are naturally produced Eicosanoid lipid mediators, which may be responsible for the effects of an inflammatory response [7]
Alpha toxinsCleave phospholipids in the cell membrane, similar to Phospholipase C. Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate [41]Bacterial pathogenesis, particularly by Clostridium perfringens. Clostridium perfringens (formerly known as Clostridium welchii) is a Gram-positive, rod-shaped anaerobic, spore-forming Bacterium [8]
Sphingomyelinase CA phosphodiesterase, cleaves phosphodiester bonds. The Sphingomyelinase Family Currently five types of SMase have been identified A phosphodiesterase is any Enzyme that breaks a Phosphodiester bond. [42]Processing of lipids such as sphingomyelin. Sphingomyelin (SPH is a type of Sphingolipid found in animal Cell membranes, especially in the membranous Myelin sheath which surrounds some Nerve [9]
Glycosyltransferases: MurG and TransglycosidasesCatalyzes the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. Glycosyltransferases are Enzymes ( EC 24) that act as a Catalyst for the transfer of a Monosaccharide unit from an activated sugar Phosphate In Chemistry, a glycosidic bond is a certain type of Functional group that joins a Carbohydrate (sugar molecule to another which may be another carbohydrate [43]Biosynthesis of disaccharides, oligosaccharides and polysaccharides (glycoconjugates), MurG is involved in bacterial peptidoglycan biosynthesis. A disaccharide is a Sugar (a Carbohydrate) composed of two Monosaccharides 'Disaccharide' is one of the four chemical groupings of carbohydrates ( An oligosaccharide is a Saccharide polymer containing a small number (typically three to ten of component sugars also known as Simple sugars. Polysaccharides are relatively complex Carbohydrates They are Polymers made up of many Monosaccharides joined together by Glycosidic bonds Not to be confused with Glycoprotein. Peptidoglycan, also known as murein, is a Polymer consisting of sugars and amino [10]
[11]
FerrochelataseConverts protoporphyrin IX into heme. Ferrochelatase (FECH protoheme ferrolyase is an enzyme that catalyses the terminal (eighth step in the biosynthesis of Heme, converting Protoporphyrin IX into In the metabolism of Porphyrin, protoporphyrin IX is created by the enzyme Protoporphyrinogen oxidase, and the enzyme Ferrochelatase converts it into A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of [44]Involved in porphyrin metabolism, protoporphyrins are used to strengthen egg shells. A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH- Protoporphyrins are Tetrapyrroles containing the following Side chains Methyl (4 Propionic acid (2 The term eggshell is a term for the outer covering of a hard-shelled egg, and some forms of eggs with soft outer coats [12]
Myotubularin-related protein familyLipid phosphatase that dephosphorylates PtdIns3P and PtdIns(3,5)P2. A phosphatase is an Enzyme that removes a Phosphate group from its Substrate by hydrolysing Phosphoric acid mono Esters into Phosphatidylinositol 3-phosphate (PtdIns3 P) is the product of both the class II and III Phosphoinositide 3-kinases (PI 3-kinases activity on Phosphatidylinositol Phosphatidylinositol (35-bisphosphate (PtdIns(35 P 2 is a minor Phospholipid component of cell membranes yet important in distinguishing cell compartments [45]Required for muscle cell differentiation. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the [13]
Dihydroorotate dehydrogenasesOxidation of dihydroorotate (DHO) to orotate. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state [46]Biosynthesis of pyrimidine nucleotides in prokaryotic and eukaryotic cells. Pyrimidine is a Heterocyclic Aromatic Organic compound similar to Benzene and Pyridine, containing two Nitrogen Atoms Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex [14]
Glycolate oxidaseCatalyses the oxidation of α-hydroxy acids to the corresponding α-ketoacids. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state α-hydroxy acids, or alpha hydroxy acids ( AHAs) are a class of chemical compounds that consist of a Carboxylic acid substituted with a hydroxy group Keto acids are organic Acids containing a Ketone Functional group and a Carboxylic acid group [47]In green plants, the enzyme participates in photorespiration. Plants are living Organisms belonging to the kingdom Plantae. Photorespiration (or "photo-respiration" is the alternate pathway for production of Glyceraldehyde 3-phosphate (G3P by RuBisCO, the main enzyme of the In animals, the enzyme participates in production of oxalate. An oxalate (also ethanedioate) is a salt or Ester of Oxalic acid. [15]

Membrane-targeting domains (“lipid clamps”)

C1 domain of PKC-delta (1ptr) Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - blue dots (cytoplasmic side). Layer of lipid phosphates - yellow dots.
C1 domain of PKC-delta (1ptr) Middle plane of the lipid bilayer - black dots. C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG as well as the analogous Boundary of the hydrocarbon core region - blue dots (cytoplasmic side). Layer of lipid phosphates - yellow dots.

Membrane-targeting domains associate specifically with head groups of their lipid ligands embedded into the membrane. These lipid ligands are present in different concentrations in distinct types of biological membranes (for example, PtdIns3P can be found mostly in membranes of early endosomes, PtdIns(3,5)P2 in late endosomes, and PtdIns4P in the Golgi). Phosphatidylinositol 3-phosphate (PtdIns3 P) is the product of both the class II and III Phosphoinositide 3-kinases (PI 3-kinases activity on Phosphatidylinositol In Biology, an endosome is a membrane-bound compartment inside cells roughly 300-400 nm in diameter when fully mature Phosphatidylinositol (35-bisphosphate (PtdIns(35 P 2 is a minor Phospholipid component of cell membranes yet important in distinguishing cell compartments In Biology, an endosome is a membrane-bound compartment inside cells roughly 300-400 nm in diameter when fully mature Phosphatidylinositol 4-phosphate (PtdIns4 P) is a precursor of Phosphatidylinositol (45-bisphosphate. The Golgi apparatus (also called the [16] Hence, each domain is targeted to a specific membrane.

Structural domains

Structural domains mediate attachment of other proteins to membranes. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby The ENTH (Epsin N-terminal homology domain a Structural domain that was found in proteins involved in Endocytosis and Cytoskeletal machinery The ANTH domain is a membrane binding domain that shows weak specificity for PtdIns(45P2. Their binding to membranes can be mediated by calcium ions (Ca2+) that form bridges between the acidic protein residues and phosphate groups of lipids, as in annexins or GLA domains. Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20

ClassFunctionPhysiologyStructure
AnnexinsCalcium-dependent intracellular membrane/ phospholipid binding. Annexin is a common name for a group of cellular Proteins The annexins are a family of proteins first described in the 1980s that bind Phospholipid membrane Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate [48]Functions include vesicle trafficking, membrane fusion and ion channel formation. A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living [28]
Synapsin ICoats synaptic vesicles and binds to several cytoskeletal elements. The synapsins are a family of Proteins that have long been implicated in the regulation of Neurotransmitter release at Synapses Specifically they are thought In a Neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various Neurotransmitters that are released during Calcium -regulated cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. [49]Functions in the regulation of neurotransmitter release. See Chemical synapse for an introduction to concepts and terminology used in this article [29]
SynucleinUnknown cellular function. Synuclein is a small soluble Protein primarily expressed in Neural tissue and in certain tumors. [50]Thought to play a role in regulating the stability and/or turnover of the plasma membrane. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Associated with both Parkinson's disease and Alzheimer's disease. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. [30]
GLA-domains of the coagulation systemGamma-carboxyglutamate (GLA) domains are responsible for the high-affinity binding of calcium ions. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby [51]Involved in function of clotting factors in the blood coagulation cascade.[31]
Spectrin and α-actinin-2Found in several cytoskeletal and microfilament proteins. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby Spectrin is a cytoskeletal Protein that lines the intracellular side of the Plasma membrane of many cell types in pentagonal or hexagonal arrangements Actinin is a Microfilament protein α-Actinin is necessary for the attachment of Actin filaments to the Z-line membrane in muscle cells Microfilaments (or actin filaments) are the thinnest filaments of the Cytoskeleton found in the cytoplasm of all Eukaryotic cells. [52]Maintenance of plasma membrane integrity and cytoskeletal structure. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer [32]

Transporters of small hydrophobic molecules

These peripheral proteins function as carriers of non-polar compounds between different types of cell membranes or between membranes and cytosolic protein complexes. The transported substances are phosphatidylinositol, tocopherol, gangliosides, glycolipids, sterol derivatives, retinol, or fatty acids.

Electron carriers

These proteins are involved in electron transport chains. Glycolipid transfer protein is a cytosolic protein that catalyses the transfer of Glycolipids between different intracellular membranes The lipocalins are a family of proteins which transport small hydrophobic molecules such as Steroids bilins Retinoids and Lipids. Retinol binding proteins are a family of Proteins with diverse functions In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Ganglioside GM2 activator protein is (GM2-AP is a lipid transfer protein that stimulates the enzymatic processing of Gangliosides, and also T-cell activation through CRAL-TRIO domain is a protein Structural domain that binds small lipophilic molecules Tocopherol, a class of chemical compounds of which many have Vitamin E activity describes a series of Organic compounds consisting of various methylated phenols Phosphatidylinositol (abbreviated PtdIns or PI is a minor Phospholipid component in the cytosolic side of eukaryotic Cell membranes. Sterol carrier proteins (also known as nonspecific lipid transfer proteins) is a family of proteins that transfer Steroids and probably also Phospholipids The steroidogenic acute regulatory protein, commonly referred to as StAR ( STARD1) is a Transport protein that regulates Cholesterol transfer An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer They include cytochrome c, cupredoxins, high potential iron protein, adrenodoxin reductase, some flavoproteins, and others. Cytochrome c, or cyt c (horse heart PDB 1HRC is a small Heme Protein found loosely associated with the inner membrane Copper proteins are Proteins that contain one or more Copper ions as Prosthetic groups The metal centres in the copper proteins can be classified into several Iron-sulfur proteins are Proteins characterized by the presence of iron-sulfur clusters containing Sulfide -linked di- tri- and tetrairon centers in variable Flavoproteins are Proteins that contain a Nucleic acid derivative of Riboflavin: the Flavin adenine dinucleotide (FAD or Flavin mononucleotide

Polypeptide hormones, toxins, and antimicrobial peptides

Many hormones, toxins, inhibitors, or antimicrobial peptides interact specifically with transmembrane protein complexes. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. Antimicrobial peptides (also called host defence peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life A transmembrane protein is a Protein that spans the entire Biological membrane. They can also accumulate at the lipid bilayer surface, prior to binding their protein targets. Such polypeptide ligands are often positively charged and interact electrostatically with anionic membranes. An ionic bond (or electrovalent bond) is a type of Chemical bond that can often form between Metal and Non-metal Ions (or An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge

Some water-soluble proteins and peptides can also form transmembrane channels. Ion channels are pore-forming Proteins that help establish and control the small Voltage Gradient across the Plasma membrane of all living They usually undergo oligomerization, significant conformational changes, and associate with membranes irreversibly. In Chemistry, an oligomer consists of a limited number of Monomer units (ολιγος or oligos is Greek for "a few" in contrast to a A macromolecule is usually flexible and dynamic It can change its shape in response to changes in its environment or other factors each possible shape is called a conformation and a transition 3D structure of one such transmembrane channel, α-hemolysin, has been determined. Hemolysis is the breakdown of Red blood cells. The ability of bacterial colonies to induce hemolysis when grown on Blood agar is used to classify certain Microorganisms In other cases, the experimental structure represents a water-soluble conformation that interacts with the lipid bilayer peripherally, although some of the channel-forming peptides are rather hydrophobic and therefore were studied by NMR spectroscopy in organic solvents or in the presence of micelles. Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is the name given to a technique which exploits the magnetic properties of certain nuclei A micelle (rarely micella, plural micelles) is an aggregate of Surfactant molecules dispersed in a liquid Colloid.

ClassProteinsPhysiology
Venom toxinsWell known types of biotoxins include neurotoxins, cytotoxins, hemotoxins and necrotoxins. This article is about the class of Biotoxins For other uses see Venom (disambiguation and Venomous (disambiguation. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low Scorpions are eight-legged Carnivorous Arthropods They are members of the order Scorpiones within the class Arachnida. Snake venom is highly modified saliva that is produced by special glands of certain species of Snakes. A conotoxin is one of a group of neurotoxic Peptides isolated from the venom of the marine Cone snail, genus Conus. Poneratoxin is a paralyzing neurotoxic Peptide from the bullet ant Paraponera clavata that affects voltage-dependent sodium ion A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels Cytotoxicity is the quality of being toxic to cells Examples of toxic agents are a Chemical substance, an Immune cell or some types of Venom Hemotoxins, haemotoxins or hematotoxins are Toxins that destroy Red blood cells (that is cause Hemolysis) disrupt Blood Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. Biotoxins have two primary functions: predation (snake, scorpion and cone snail toxins) and defense (honeybee and ant toxins). A snake is an elongate Reptile of the suborder Serpentes Like all reptiles snakes are covered in scales. Scorpions are eight-legged Carnivorous Arthropods They are members of the order Scorpiones within the class Arachnida. The cone snails or cone shells, sometimes simply known as "cones" (family Conidae) are a Taxonomic family of medium-sized to large sophisticated This article refers collectively to all true honey bees for the "common" domesticated honey bee see European honey bee Honey bees Ants are social Insects of the family Formicidae and along with the related families of Wasps and Bees belong to the order [53]
Sea anemone toxinsInhibition of sodium and potassium channels and membrane pore formation are the primary actions of over 40 known Sea anemone peptide toxins. Sea anemones are a group of water dwelling predatory animals of the order Actiniaria; they are named after the Anemone, a terrestrial Flower Sodium channels are Integral membrane proteins that form Ion channels, conducting sodium ions ( Na+) through a cell's Plasma membrane A neurotoxin is a Toxin that acts specifically on nerve cells ( Neurons, usually by interacting with Membrane proteins such as Ion channels Cytolysin refers to the substance or Antibody elaborated by microorganisms plants or animals that is specifically toxic to individual cells, in many cases causing In the field of Cell biology, potassium channels are the most widely distributed type of Ion channel and are found in virtually all living organisms Pore forming toxins (PFTs are Protein Toxins, typically (but not exclusively produced by Bacteria, such as ''C Sea anemone are carnivorous animals and use toxins in predation and defense; anemone toxin is of similar toxicity as the most toxic organophosphate chemical warfare agents. A carnivore (ˈkɑrnɪvɔər meaning 'meat eater' ( Latin carne meaning 'flesh' and vorare meaning 'to devour' is any animal with a diet consisting Toxicity is the degree to which a substance is able to damage an exposed organism An organophosphate (sometimes abbreviated OP) is the general name for Esters of Phosphoric acid. Chemical warfare involves using the toxic properties of Chemical substances to kill injure or incapacitate an enemy. [54]
Bacterial toxinsMicrobial toxins are the primary virulence factors for a variety of pathogenic bacteria. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Clostridium perfringens (formerly known as Clostridium welchii) is a Gram-positive, rod-shaped anaerobic, spore-forming Bacterium Botulinum toxin is a Neurotoxin Protein produced by the Bacterium Clostridium botulinum. An enterotoxin (not to be confused with Endotoxin) is a Protein Toxin released by a Microorganism in the Intestine. Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. Bacteriocins are Proteinaceous Toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s Microcins are very small Bacteriocins composed of a relatively few Peptides For this reason they are distinct from their larger Protein cousins Lantibiotics are a class of Peptide Antibiotics that contain polycyclic Thioether Amino acids as well as the unsaturated amino acids Nisin is a polycyclic Peptide antibacterial with 34 Amino acid residues used as a food Preservative. Gramicidin S or Gramicidin Soviet is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi A microorganism (also spelled micro organism or micro-organism and also called a microbe) is an Organism that is Microscopic (usually Virulence factors are molecules produced by a Pathogen that specifically cause disease or that influence their host's function to allow the pathogen to thrive A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Some toxins, are Pore forming toxins that lyse cellular membranes. Pore forming toxins (PFTs are Protein Toxins, typically (but not exclusively produced by Bacteria, such as ''C Other toxins inhibit protein synthesis or activate second messenger pathways causing dramatic alterations to signal transduction pathways critical in maintaining a variety of cellular functions. Protein biosynthesis (synthesis is the process in which cells build Proteins The term is sometimes used to refer only to protein translation but more In Cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signaling whereby a diffusable signaling molecule In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another Several bacterial toxins can act directly on the immune system, by acting as superantigens and causing massive T cell proliferation, which overextends the immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Superantigens (SAgs are secreted proteins ( Exotoxins) that exhibit highly potent lymphocyte-transforming ( Mitogenic activity directed towards T Lymphocytes T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. The term cell growth is used in two different ways in Biology. Botulinum toxin is a neurotoxin that prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane, inhibiting neurotransmitter release. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands See Chemical synapse for an introduction to concepts and terminology used in this article [55]
Fungal ToxinsThese peptides are characterized by the presence of an unusual amino acid, α-aminoisobutyric acid, and exhibit antibiotic and antifungal properties due to their membrane channel-forming activities. A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ A lipopeptide is a Molecule consisting of a Lipid connected to a Peptide. Surfactin is a very powerful Surfactant commonly used as an Antibiotic. Daptomycin is a novel Lipopeptide Antibiotic used in the treatment of certain infections caused by Gram-positive organisms 2-Aminoisobutyric acid, or α-aminoisobutyric acid ( AIB) or α-methylalanine or 2-methylalanine, is an Amino acid with the Structural In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa An antifungal drug is Medication used to treat fungal Infections such as Athlete's foot, Ringworm, Candidiasis (thrush [56]
Antimicrobial peptidesThe modes of action by which antimicrobial peptides kill bacteria is varied and includes disrupting membranes, interfering with metabolism, and targeting cytoplasmic components. Antimicrobial peptides (also called host defence peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life Helicobacter pylori ( is a Gram-negative, microaerophilic Bacterium that inhabits various areas of the stomach and Duodenum. Lactoferricin is an Amphipathic, Cationic Peptide with anti- Microbial and anti- Cancer properties Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In contrast to many conventional antibiotics these peptides appear to be bacteriocidal instead of bacteriostatic. A bactericide or bacteriocide is a substance that kills bacteria and preferably nothing else Bacteriostatic Antibiotics limit the growth of bacteria by interfering with bacterial Protein production DNA replication or other aspects of
DefensinsDefensins are a type of antimicrobial peptide; and are an important component of virtually all innate host defenses against microbial invasion. Defensins are small (15-20 residue) Cysteine -rich Cationic Proteins found in both Vertebrates and Invertebrates They are Cyclotides are small Disulfide rich Peptides isolated from plants Thionin, also known as thionin acetate or Lauth's violet, is a strongly staining metachromatic dye that are widely used for biological staining Immune system|Adaptive immune systemThe innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner Defensins penetrate microbial cell membranes by way of electrical attraction, and form a pore in the membrane allowing efflux, which ultimately leads to the lysis of microorganisms. [57]
Neuronal peptides
  • Tachykinin peptides[67]
These proteins excite neurons, evoke behavioral responses, are potent vasodilatators, and are responsible for contraction in many types of smooth muscle. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Behavior or behaviour (see spelling differences) refers to the actions or Reactions of an object or Organism, usually Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder [58]
Apoptosis regulatorsMembers of the Bcl-2 family govern mitochondrial outer membrane permeability. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Bcl-2 itself suppresses apoptosis in a variety of cell types including lymphocytes and neuronal cells. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information

See also

References

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  31. ^ Darkes MJM, Davies SMA, Bradshaw JP (1997). "Interaction of tachykinins with phospholipid membranes: A neutron diffraction study". Physica B 241: 1144–7. doi:10.1016/S0921-4526(97)00811-9. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  32. ^ Ellena JF, Moulthrop J, Wu J, Rauch M, Jaysinghne S, Castle JD, Cafiso DS. (Nov 2004). "Membrane position of a basic aromatic peptide that sequesters phosphatidylinositol 4,5 bisphosphate determined by site-directed spin labeling and high-resolution NMR. ". Biophys J. 87 (5): 3221-33. doi:10.1529/biophysj.104.046748. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15315949.  
  33. ^ Marcotte I, Dufourc E, Ouellet M, Auger M (2003). "Interaction of the neuropeptide met-enkephalin with zwitterionic and negatively charged bicelles as viewed by 31P and 2H solid-state NMR". Biophys J 85 (1): 328-39. PMID 12829487.  
  34. ^ Zhang W, Crocker E, McLaughlin S, Smith S (2003). "Binding of peptides with basic and aromatic residues to bilayer membranes: phenylalanine in the myristoylated alanine-rich C kinase substrate effector domain penetrates into the hydrophobic core of the bilayer". J Biol Chem 278 (24): 21459-66. doi:10.1074/jbc.M301652200. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12670959.  
  35. ^ Pfam entry Abhydrolase 1
  36. ^ Pfam entry: Phospholipase A2
  37. ^ Pfam entry: Phosphatidylinositol-specific phospholipase C, X domain
  38. ^ Pfam entry: Cholesterol oxidase
  39. ^ Pfam entry: Retinal pigment epithelial membrane protein
  40. ^ Pfam entry: Lipoxygenase
  41. ^ PDBsum entry: Alpha Toxin
  42. ^ Pfam entry: Type I phosphodiesterase
  43. ^ Pfam entry: Glycosyl transferases group 1
  44. ^ Pfam entry: Ferrochelatase
  45. ^ Pfam entry:Myotubularin-related
  46. ^ Pfam entry:Dihydroorotate dehydrogenase
  47. ^ Pfam entry: FMN-dependent dehydrogenase
  48. ^ Pfam entry: Annexin
  49. ^ Pfam entry Synapsin N
  50. ^ Pfam entry Synuclein
  51. ^ Pfam entry: Gla
  52. ^ Pfam entry Spectrin
  53. ^ Herv ̌Rochat, Marie-France Martin-Eauclaire (editors) (2000). Animal toxins: facts and protocols. Basel: Birkhũser Verlag. ISBN 3-7643-6020-8.  
  54. ^ Patocka, Jiri and Anna Strunecka. (1999) Sea Anemone Toxins. The ASA Newsletter.
  55. ^ Schmitt C, Meysick K, O'Brien A. "Bacterial toxins: friends or foes?". Emerg Infect Dis 5 (2): 224-34. PMID 10221874.  
  56. ^ Chugh J, Wallace B (2001). "Peptaibols: models for ion channels". Biochem Soc Trans 29 (Pt 4): 565-70. doi:10.1042/BST0290565. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11498029.  
  57. ^ Oppenheim1, J J, A Biragyn2, L W Kwak2 and D Yang (2003). "Roles of antimicrobial peptides such as defensins in innate and adaptive immunity". Annals of the Rheumatic Diseases 62: ii17. PMID 14532141.  
  58. ^ Pfam entry Tachykinin

General references

External links

Orientations of Proteins in Membranes (OPM database provides spatial positions of protein three-dimensional structures with respect to the Lipid bilayer.
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