Peripheral membrane protein

Source: Wikipedia, the free encyclopedia.
(Redirected from
Peripheral protein
)

Peripheral membrane proteins, or extrinsic membrane proteins,

GPI anchors
are an exception to this rule and can have purification properties similar to those of integral membrane proteins.

The reversible attachment of proteins to biological membranes has shown to regulate

substrate(s).[3] Membrane binding may also promote rearrangement, dissociation, or conformational changes within many protein structural domains, resulting in an activation of their biological activity.[4][5] Additionally, the positioning of many proteins are localized to either the inner or outer surfaces or leaflets of their resident membrane.[6]
This facilitates the assembly of multi-protein complexes by increasing the probability of any appropriate
protein–protein interactions
.

ionic interactions
with membrane lipids (e.g. through a calcium ion)

Binding 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.

Peripheral membrane proteins may interact with other proteins or directly with the lipid bilayer. In the latter case, they are then known as amphitropic proteins.[4] Some proteins, such as

neurotoxins
accumulate at the membrane surface prior to locating and interacting with their cell surface receptor targets, which may themselves be peripheral membrane proteins.

The

Å, although this may be wider in biological membranes that include large amounts of gangliosides or lipopolysaccharides.[7]
The hydrophobic inner core region of typical
Small angle X-ray scattering (SAXS).[8]
The boundary region between the hydrophobic inner core and the hydrophilic interfacial regions is very narrow, at around 3 Å, (see lipid bilayer article for a description of its component chemical groups). 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 2 M.[9][10] 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.[11]

Some water-soluble proteins associate with lipid bilayers irreversibly and can form transmembrane alpha-helical or

BcL-2 like protein , in some amphiphilic antimicrobial peptides , and in certain annexins . These proteins are usually described as peripheral as one of their conformational states is water-soluble or only loosely associated with a membrane.[12]

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.

The association of a protein with a

quaternary structures or oligomeric complexes, and specific binding of ions, ligands, or regulatory lipids
.

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 surface of a protein,

covalently bound lipid anchors
.

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.[14]

amphitropic proteins bind to hydrophobic anchor structures

Non-specific hydrophobic association

Amphitropic proteins associate with lipid bilayers via various

MARCKS protein or histactophilin, when their natural hydrophobic anchors are present. [15]

Covalently bound lipid anchors

protein crystallographic studies
.

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.

Some

glutamate residues of the protein and lipid phosphates via intervening calcium ions (Ca2+). 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
..

Protein–lipid electrostatic interactions

Any positively charged protein will be attracted to a negatively charged membrane by nonspecific

PH domains, C1 domains, and C2 domains
.

Electrostatic interactions are strongly dependent on the

0.14M NaCl): ~3 to 4 kcal/mol for small cationic proteins, such as cytochrome c, charybdotoxin or hisactophilin.[15][19][20]

Spatial position in membrane

Orientations and penetration depths of many amphitropic proteins and peptides in membranes are studied using

NMR spectroscopy,[24]
ATR
FTIR spectroscopy,[25] X-ray or neutron diffraction,[26] and computational methods.[27][28][29][30]

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,

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.[34][35][36]

Categories

Enzymes

Peripheral enzymes participate in

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

Class Function Physiology Structure
Alpha/beta hydrolase fold
 Catalyzes the hydrolysis of chemical bonds.[37] Includes
fungal, gastric and pancreatic lipases, palmitoyl protein thioesterases, cutinase, and cholinesterases
 central beta sheet inserted in between two layers of alpha helices[38]
Phospholipase A2 (secretory and cytosolic) Hydrolysis of sn-2 fatty acid bond of phospholipids.[39] Lipid digestion, membrane disruption, and lipid signaling. contains catalytic amino acid triad: aspartic acid, serine, and histidine[40]
Phospholipase C Hydrolyzes PIP2, a
inositol triphosphate and diacylglycerol.[41]
 Lipid signaling core structure composed of a split triosephosphate isomerase (TIM) barrel which has an active site, catalytic residues, and a Ca2+ binding site [42]
Cholesterol oxidases
Oxidizes and isomerizes cholesterol to cholest-4-en-3-one.[43]
 Depletes
cellular membranes of cholesterol, used in bacterial pathogenesis
.		 two loops of residue which act as a lid on the active site[44]
Carotenoid oxygenase Cleaves
carotenoids.[45]
 Carotenoids function in both plants and animals as
flavors
, floral scents and defense compounds.		 composed of multiple enzymes attached together forming branch-like structures[46]
Lipoxygenases
catalyze the dioxygenation of polyunsaturated fatty acids.[47]
 In animals lipoxygenases are involved in the synthesis of
leukotrienes
.		 hundreds of amino acids that makes up a protein are organized into two domains: beta-sheet N terminal and helical C terminal[48]
Alpha toxins Cleave phospholipids in the cell membrane, similar to Phospholipase C.[49] Bacterial pathogenesis, particularly by Clostridium perfringens. soluble monomer with oligomeric pre-pore complexes[50]
Sphingomyelinase
C		 A phosphodiesterase, cleaves phosphodiester bonds.[51] Processing of lipids such as sphingomyelin. saposin domain and connector regions with a metallophosphate catalytic domain [52]
Glycosyltransferases: MurG and Transglycosidases Catalyzes the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming
glycosidic bonds.[53]
 Biosynthesis of disaccharides, oligosaccharides and polysaccharides (glycoconjugates), MurG is involved in bacterial peptidoglycan biosynthesis. three glycine rich loops: one in the C terminal and two in the N terminal [54]
Ferrochelatase Converts protoporphyrin IX into heme.[55] Involved in
egg shells
.
helices[56]
Myotubularin-related protein family Lipid
PtdIns(3,5)P2.[57]
 Required for muscle cell differentiation. contains a GRAM domain, SET interacting domain, and a PDZ binding domain[58]
Dihydroorotate dehydrogenases
Oxidation of dihydroorotate (DHO) to orotate.[59]
 Biosynthesis of
eukaryotic
cells.		 composed of two domains:
alpha-helical domain that forms the opening tunnel to the active site [60]
Glycolate oxidase
 Catalyses the
ketoacids.[61]
 In green plants, the enzyme participates in photorespiration. In animals, the enzyme participates in production of oxalate. β8/α8 fold containing alpha helices, beta strands, and loops and turns[62]

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.

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,

PtdIns(3,5)P2 in late endosomes, and PtdIns4P in the Golgi).[18]
Hence, each domain is targeted to a specific membrane.

Structural domains

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.

Class Function Physiology Structure
Annexins Calcium-dependent intracellular membrane/ phospholipid binding.[63] Functions include
vesicle trafficking, membrane fusion and ion channel
formation.
Synapsin I Coats
cytoskeletal elements.[64]
 Functions in the regulation of neurotransmitter release.
Synuclein Unknown cellular function.[65] 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
.
GLA-domains of the coagulation system
Gamma-carboxyglutamate (GLA) domains are responsible for the high-affinity binding of calcium ions.[66]
 Involved in function of clotting factors in the blood coagulation cascade.
Spectrin and α-actinin-2 Found in several cytoskeletal and microfilament proteins.[67] Maintenance of
plasma membrane
integrity and cytoskeletal structure.

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, fatty acids, water, macromolecules, red blood cells, phospholipids, and nucleotides.

Electron carriers

These proteins are involved in

high potential iron protein, adrenodoxin reductase, some flavoproteins
, and others.

Polypeptide hormones, toxins, and antimicrobial peptides

Many hormones,

anionic
membranes.

Some water-soluble proteins and peptides can also form

micelles
.

Class Proteins Physiology
Venom toxins Well known types of biotoxins include
honeybee and ant toxins).[68]
Sea anemone toxins Inhibition of sodium and
carnivorous animals and use toxins in predation and defense; anemone toxin is of similar toxicity as the most toxic organophosphate chemical warfare agents.[69]
Bacterial
toxins
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.[70]
Fungal
toxins		 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.[71]
Antimicrobial peptides
 The modes of action by which antimicrobial peptides kill bacteria is varied and includes disrupting membranes, interfering with
bacteriostatic
.
Defensins
  • Insect defensins
  • Cyclotides and thionins
 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.[72]
Neuronal
peptides
  • Tachykinin
    peptides
 These proteins excite neurons, evoke
behavioral responses, are potent vasodilatators, and are responsible for contraction in many types of smooth muscle.[73]
Apoptosis regulators Members of the Bcl-2 family govern
neuronal cells
.

See also

References

  1. ^ "extrinsic protein | biology | Britannica". www.britannica.com. Retrieved 2022-07-04.
  2. ISBN 3-527-31151-3
    .
  3. PMID 16814865
    .
  4. ^
    PMID 10503244
    .
  5. PMID 16650855
    .
  6. S2CID 36940600
    .
  7. ISBN 978-0-12-643871-0
    .
  8. PMID 15016920
    .
  9. PMID 11438731
    .
  10. S2CID 36212541
    .
  11. PMID 11063882
    .
  12. S2CID 20892603
    .
  13. PMID 12719487
    .
  14. PMID 16689633
    .
  15. ^
    PMID 8780505
    .
  16. ISBN 978-0-12-643871-0
    .
  17. ISBN 978-0-444-51139-3
    .
  18. ^
    PMID 15869386
    .
  19. PMID 9336168
    .
  20. ISBN 0-444-81575-9
    .
  21. PMID 15869384
    .
  22. PMID 10551860
    .
  23. PMID 11258945
    .
  24. PMID 11230696
    .
  25. PMID 16055150
    .
  26. ^
    PMID 10388560
    .
  27. PMID 11804593
    .
  28. PMID 15379706
    .
  29. PMID 16731967
    .
  30. ^ Lomize A, Lomize M, Pogozheva I. "Comparison with experimental data". Orientations of Proteins in Membranes. University of Michigan. Retrieved 2007-02-08.
  31. PMID 52374
    .
  32. PMID 15519307
    .
  33. doi:10.1016/S0921-4526(97)00811-9
    .
  34. PMID 15315949
    .
  35. PMID 12829487
    .
  36. PMID 12670959
    .
  37. ^ "Pfam entry Abhydrolase 1". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  38. ISSN 1742-464X
    .
  39. ^ "Pfam entry: Phospholipase A2". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  40. PMID 30521272
    , retrieved 2023-11-29
  41. ^ "Pfam entry: Phosphatidylinositol-specific phospholipase C, X domain". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  42. ^ "Phospholipase C", Wikipedia, 2023-08-16, retrieved 2023-11-29
  43. ^ "Pfam entry: Cholesterol oxidase". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  44. ISSN 0006-2960
    .
  45. ^ "Pfam entry: Retinal pigment epithelial membrane protein". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  46. ^ "Carotenoid oxygenase", Wikipedia, 2023-11-29, retrieved 2023-11-29
  47. ^ "Pfam entry: Lipoxygenase". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  48. ISSN 0300-9084
    .
  49. ^ PDBsum entry: Alpha Toxin
  50. ^ "Alpha Toxin - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-11-29.
  51. ^ "Pfam entry: Type I phosphodiesterase". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  52. ISSN 0022-2836
    .
  53. ^ "Pfam entry: Glycosyl transferases group 1". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  54. ISSN 0959-440X
    .
  55. ^ "Pfam entry: Ferrochelatase". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  56. ISSN 0969-2126
    .
  57. ^ "Pfam entry:Myotubularin-related". Archived from the original on 2007-09-26. Retrieved 2007-01-25.
  58. ^ "Emery and Rimoin's Principles and Practice of Medical Genetics". ScienceDirect. Retrieved 2023-11-29.
  59. ^ "Pfam entry:Dihydroorotate dehydrogenase". Archived from the original on 2007-09-26. Retrieved 2007-01-25.
  60. ISSN 0969-2126
    .
  61. ^ "Pfam entry: FMN-dependent dehydrogenase". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  62. ^ "Glycolate oxidase - Proteopedia, life in 3D". proteopedia.org. Retrieved 2023-11-28.
  63. ^ "Pfam entry: Annexin". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  64. ^ "Pfam entry Synapsin N". Archived from the original on 2007-09-26. Retrieved 2007-01-25.
  65. ^ "Pfam entry Synuclein". Archived from the original on 2007-09-26. Retrieved 2007-01-25.
  66. ^ "Pfam entry: Gla". Archived from the original on 2007-09-29. Retrieved 2007-01-25.
  67. ^ "Pfam entry Spectrin". Archived from the original on 2007-09-26. Retrieved 2007-01-25.
  68. ISBN 3-7643-6020-8
    .
  69. ^ Patocka J, Strunecka A (1999). "Sea Anemone Toxins". The ASA Newsletter. Archived from the original on 15 June 2013.
  70. PMID 10221874
    .
  71. PMID 11498029
    .
  72. PMID 14532141
    .
  73. ^ "Pfam entry Tachykinin". Archived from the original on 2007-09-26. Retrieved 2007-01-25.

Further reading

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Peripheral_membrane_protein&oldid=1215183656"