بروتين غشائي محيطي

البروتينات الغشائية المحيطية Peripheral membrane proteins جزيئات بروتينية ترتبط بشكل ضعيف بالغشاء الحيوي ولا تمتد ضمن القلب الدسم للغشاء الحيوي ، لكنها ترتبط بشكل غير مباشر غالبا عن طريق الارتباط بالبروتينات المدمجة أوعن طريق الارتباط بالرؤوس القطبية لجزيئات الدسم. الكثير من الوحدات البروتينية المنظمة regulatory protein subunits للقنوات الشاردية ion channel أوللمستقبلات عبر-غشائية مثلا يمكن حتى تصنف على انها بروتينات غشائية محيطية .

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)

إلتصاق البروتينات الجانبية بطبقة الدهن الثنائية

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.

آليات الالتصاق بالأغشية

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.

ارتباطات بروتين-دهن معينة

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.

أصناف البروتينات الجانبية

الإنزيمات

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). Lipases can also digest lipids that form micelles or nonpolar droplets in water.

الرتبة	الوظيفة	فيسيولوجي	البنية
Alpha/beta hydrolase fold	Catalyzes the hydrolysis of chemical bonds.	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.	Lipid digestion, membrane disruption, and lipid signaling.	[2] [3]
Phospholipase C	Hydrolyzes PIP2, a phosphatidylinositol, into two second messagers, inositol triphosphate and diacylglycerol.	Lipid signaling	[4]
Cholesterol oxidases	Oxidizes and isomerizes cholesterol to cholest-4-en-3-one.	Depletes cellular membranes of cholesterol, used in bacterial pathogenesis.	[5]
Carotenoid oxygenase	Cleaves carotenoids.	Carotenoids function in both plants and animals as hormones (includes vitamin A in humans), pigments, flavors, floral scents and defense compounds.	[6]
Lipoxygenases	Iron-containing enzymes that catalyze the dioxygenation of polyunsaturated fatty acids.	In animals lipoxygenases are involved in the synthesis of inflammatory mediators known as leukotrienes.	[7]
Alpha toxins	Cleave phospholipids in the cell membrane, similar to Phospholipase C.	Bacterial pathogenesis, particularly by Clostridium perfringens.	[8]
Sphingomyelinase C	A phosphodiesterase, cleaves phosphodiester bonds.	Processing of lipids such as sphingomyelin.	[9]
Glycosyltransferases: MurG and Transglycosidases	Catalyzes the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds.	Biosynthesis of disaccharides, oligosaccharides and polysaccharides (glycoconjugates), MurG is involved in bacterial peptidoglycan biosynthesis.	[10] [11]
Ferrochelatase	Converts protoporphyrin IX into heme.	Involved in porphyrin metabolism, protoporphyrins are used to strengthen egg shells.	[12]
Myotubularin-related protein family	Lipid phosphatase that dephosphorylates PtdIns3P and PtdIns(3,5)P2.	Required for muscle cell differentiation.	[13]
Dihydroorotate dehydrogenases	Oxidation of dihydroorotate (DHO) to orotate.	Biosynthesis of pyrimidine nucleotides in prokaryotic and eukaryotic cells.	[14]
Glycolate oxidase	Catalyses the oxidation of α-hydroxy acids to the corresponding α-ketoacids.	In green plants, the enzyme participates in photorespiration. In animals, the enzyme participates in production of oxalate.	[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.

النطاقات البنيوية

Structural domains mediate attachment of other proteins to membranes. 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.

الرتبة	الوظيفة	الفيسيولوجيا	البنية
Annexins	Calcium-dependent intracellular membrane/ phospholipid binding.	Functions include vesicle trafficking, membrane fusion and ion channel formation.	[16]
Synapsin I	Coats synaptic vesicles and binds to several cytoskeletal elements.	Functions in the regulation of neurotransmitter release.	[17]
Synuclein	Unknown cellular function.	Thought to play a role in regulating the stability and/or turnover of the plasma membrane. Associated with both Parkinson's disease and Alzheimer's disease.	[18]
GLA-domains of the coagulation system	Gamma-carboxyglutamate (GLA) domains are responsible for the high-affinity binding of calcium ions.	Involved in function of clotting factors in the blood coagulation cascade.	[19]
Spectrin and α-actinin-2	Found in several cytoskeletal and microfilament proteins.	Maintenance of plasma membrane integrity and cytoskeletal structure.	[20]

هورمونات عديدة الپپتيد وسميات وپپتيدات مضادة للجراثيم

الرتبة	پروتينات	فيسيولوجيا
Venom toxins	سم العقرب[21] Snake venom[22] Conotoxins[23] Poneratoxin (insect)[24]	Well known types of biotoxins include neurotoxins, cytotoxins, hemotoxins and necrotoxins. Biotoxins have two primary functions: predation (ثعبان, scorpion and cone snail toxins) and defense (نحل العسل and نمل toxins).
Sea anemone toxins	Sea anemone sodium channel inhibitory toxin [25] Neurotoxin III [26] Cytolysins [27]	Inhibition of sodium and potassium channels and membrane pore formation are the primary actions of over 40 known Sea anemone peptide toxins. 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.
Bacterial toxins	Perfringolysin O[28] Botulinum toxin B [29] Heat-stable enterotoxin B[30] δ-Endotoxins [31] Bacteriocins [32] (see microcin) Lantibiotic peptides [33] (see nisin) Gramicidin S [34]	Microbial toxins are the primary virulence factors for a variety of pathogenic bacteria. Some toxins, are Pore forming toxins that lyse cellular membranes. 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. 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. Botulinum toxin is a neurotoxin that prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane, inhibiting neurotransmitter release.
Fungal Toxins	Cyclic lipopeptide antibiotics Surfactin and daptomycin[35] Peptaibols [36]	These 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.
Antimicrobial peptides	HP peptide[37] Saposin B and NK-lysin [38] Lactoferricin B [39] Magainin [40], Moricins [41], and Pleurocidin [42]	The modes of action by which antimicrobial peptides kill bacteria is varied and includes disrupting membranes, interfering with metabolism, and targeting cytoplasmic components. In contrast to many conventional antibiotics these peptides appear to be bacteriocidal instead of bacteriostatic.
Defensins	Insect defensins[43] Plant defensins[44]: Cyclotides [45] and thionins [46]	Defensins are a type of antimicrobial peptide; and are an important component of virtually all innate host defenses against microbial invasion. 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.
Neuronal peptides	Tachykinin peptides[47]	These proteins excite neurons, evoke behavioral responses, are potent vasodilatators, and are responsible for contraction in many types of smooth muscle.
Apoptosis regulators	Bcl-2 [48]	Members of the Bcl-2 family govern mitochondrial outer membrane permeability. Bcl-2 itself suppresses apoptosis in a variety of cell types including lymphocytes and neuronal cells.

انظر أيضاً

Membrane proteins
Lipoproteins
Transmembrane proteins
Antimicrobial peptides

هامش

^ Pfam entry Abhydrolase 1
^ Pfam entry: Phospholipase A2
^ Pfam entry: Phosphatidylinositol-specific phospholipase C, X domain
^ Pfam entry: Cholesterol oxidase
^ Pfam entry: Retinal pigment epithelial membrane protein
^ Pfam entry: Lipoxygenase
^ PDBsum entry: Alpha Toxin
^ Pfam entry: Type I phosphodiesterase
^ Pfam entry: Glycosyl transferases group 1
^ Pfam entry: Ferrochelatase
^ Pfam entry:Myotubularin-related
^ Pfam entry:Dihydroorotate dehydrogenase
^ Pfam entry: FMN-dependent dehydrogenase
^ Pfam entry: Annexin
^ Pfam entry Synapsin N
^ Pfam entry Synuclein
^ Pfam entry: Gla
^ Pfam entry Spectrin
^ Herv ̌Rochat, Marie-France Martin-Eauclaire (editors) (2000). . Basel: Birkhũser Verlag. ISBN .CS1 maint: extra text: authors list (link)
^ Patocka, Jiri and Anna Strunecka. (1999) Sea Anemone Toxins. The ASA Newsletter.
^ Schmitt C, Meysick K, O'Brien A. "Bacterial toxins: friends or foes?". Emerg Infect Dis. 5 (2): 224–34. PMID 10221874.CS1 maint: multiple names: authors list (link)
^ Chugh J, Wallace B (2001). "Peptaibols: models for ion channels" (PDF). Biochem Soc Trans. 29 (Pt 4): 565–70. doi:10.1042/BST0290565. PMID 11498029.
^ 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.CS1 maint: multiple names: authors list (link)
^ Pfam entry Tachykinin

مصادر عامة

Lukas K. Tamm (Editor). . Chichester: John Wiley & Sons. ISBN .CS1 maint: extra text: authors list (link)
Cho, W. and Stahelin, R.V. (2005). "Membrane-protein interactions in cell signaling and membrane trafficking". Annual Review of Biophysics and Biomolecular Structure. 34: 119–151. doi:10.1146/annurev.biophys.33.110502.133337. Retrieved 2007-01-23. Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Goni F.M. (2002). "Non-permanent proteins in membranes: when proteins come as visitors" (PDF). Mol. Membr. Biol. 19: 237–245. doi:10.1080/0968768021000035078.
Johnson J, Cornell R (1999). "Amphitropic proteins: regulation by reversible membrane interactions (review)" (PDF). Mol Membr Biol. 16 (3): 217–35. doi:10.1080/096876899294544. PMID 10503244.
Seaton B.A. and Roberts M.F. Peripheral membrane proteins. pp. 355-403. In Biological Membranes (Eds. K. Mertz and B.Roux), Birkhauser Boston, 1996.
Benga G. Protein-lipid interactions in biological membranes, pp.159-188. In Structure and Properties of Biological Membranes, vol. 1 (Ed. G. Benga) Boca Raton CRC Press, 1985.
Kessel A. and Ben-Tal N. 2002. Free energy determinants of peptide association with lipid bilayers. In Current Topics in Membranes 52: 205-253.
Malmberg N, Falke J (2005). "Use of EPR power saturation to analyze the membrane-docking geometries of peripheral proteins: applications to C2 domains". Annu Rev Biophys Biomol Struct. 34: 71–90. doi:10.1146/annurev.biophys.34.040204.144534. PMID 15869384.
McIntosh T, Simon S (2006). "Roles of bilayer material properties in function and distribution of membrane proteins". Annu Rev Biophys Biomol Struct. 35: 177–98. doi:10.1146/annurev.biophys.35.040405.102022. PMID 16689633.