Membrane protein

Membrane protein complexes of photosynthesis in the thylakoid membrane

Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane and can either penetrate the membrane (transmembrane) or associate with one or the other side of a membrane (integral monotopic). Peripheral membrane proteins are transiently associated with the cell membrane.

Membrane proteins are common, and medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs.<ref name="pmid17139284">Template:Cite journal</ref> Nonetheless, compared to other classes of proteins, determining membrane protein structures remains a challenge in large part due to the difficulty in establishing experimental conditions that can preserve the correct (native) conformation of the protein in isolation from its native environment.

FunctionEdit

Membrane proteins perform a variety of functions vital to the survival of organisms:<ref>Template:Cite journal</ref>

Membrane receptor proteins relay signals between the cell's internal and external environments.
Transport proteins move molecules and ions across the membrane. They can be categorized according to the Transporter Classification database.
Membrane enzymes may have many activities, such as oxidoreductase, transferase or hydrolase.<ref>Template:Cite journal Template:Open access</ref>
Cell adhesion molecules allow cells to identify each other and interact. For example, proteins involved in immune response

The localization of proteins in membranes can be predicted reliably using hydrophobicity analyses of protein sequences, i.e. the localization of hydrophobic amino acid sequences.

Integral membrane proteinsEdit

File:Polytopic membrane protein.png

Schematic representation of transmembrane proteins: 1. a single transmembrane α-helix (bitopic membrane protein) 2. a polytopic transmembrane α-helical protein 3. a polytopic transmembrane β-sheet protein
The membrane is represented in light-brown.

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Integral membrane proteins are permanently attached to the membrane. Such proteins can be separated from the biological membranes only using detergents, nonpolar solvents, or sometimes denaturing agents.Template:Cn They can be classified according to their relationship with the bilayer:

Integral polytopic proteins are transmembrane proteins that span across the membrane more than once. These proteins may have different transmembrane topology.<ref>Template:Cite journal</ref><ref name="Karp2009">Template:Cite book</ref> These proteins have one of two structural architectures:
- Helix bundle proteins, which are present in all types of biological membranes;
- Beta barrel proteins, which are found only in outer membranes of Gram-negative bacteria, and outer membranes of mitochondria and chloroplasts.<ref name="Selkrig2014">Template:Cite journal</ref>
Bitopic proteins are transmembrane proteins that span across the membrane only once. Transmembrane helices from these proteins have significantly different amino acid distributions to transmembrane helices from polytopic proteins.<ref>Template:Cite journal Template:Open access</ref>
Integral monotopic proteins are integral membrane proteins that are attached to only one side of the membrane and do not span the whole way across.

Peripheral membrane proteinsEdit

File:Monotopic membrane protein.svg

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 hydrophobic loop 3. interaction by a covalently bound membrane lipid (lipidation) 4. electrostatic or ionic interactions with membrane lipids (e.g. through a calcium ion)

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Peripheral membrane proteins are temporarily attached either to the lipid bilayer or to integral proteins by a combination of hydrophobic, electrostatic, and other non-covalent interactions. Peripheral proteins dissociate following treatment with a polar reagent, such as a solution with an elevated pH or high salt concentrations.Template:Cn

Integral and peripheral proteins may be post-translationally modified, with added fatty acid, diacylglycerol<ref name="pmid29695868">Template:Cite journal</ref> or prenyl chains, or GPI (glycosylphosphatidylinositol), which may be anchored in the lipid bilayer.

Polypeptide toxinsEdit

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Polypeptide toxins and many antibacterial peptides, such as colicins or hemolysins, and certain proteins involved in apoptosis, are sometimes considered a separate category. These proteins are water-soluble but can undergo significant conformational changes, form oligomeric complexes and associate irreversibly or reversibly with the lipid bilayer.Template:Cn

In genomesEdit

Membrane proteins, like soluble globular proteins, fibrous proteins, and disordered proteins, are common.<ref>Template:Cite journal</ref> It is estimated that 20–30% of all genes in most genomes encode for membrane proteins.<ref name=":0">Template:Cite journal</ref><ref>Template:Cite journal Template:Open access</ref> For instance, about 1000 of the ~4200 proteins of E. coli are thought to be membrane proteins, 600 of which have been experimentally verified to be membrane resident.<ref name="Daley">Template:Cite journal Template:Open access</ref> In humans, current thinking suggests that fully 30% of the genome encodes membrane proteins.<ref name=":1">Template:Cite journal Template:Open access</ref>

In diseaseEdit

Membrane proteins are the targets of over 50% of all modern medicinal drugs.<ref name="pmid17139284"/> Among the human diseases in which membrane proteins have been implicated are heart disease, Alzheimer's and cystic fibrosis.<ref name=":1" />

Purification of membrane proteinsEdit

Although membrane proteins play an important role in all organisms, their purification has historically, and continues to be, a huge challenge for protein scientists. In 2008, 150 unique structures of membrane proteins were available,<ref>Template:Cite journal</ref> and by 2019 only 50 human membrane proteins had had their structures elucidated.<ref name=":1" /> In contrast, approximately 25% of all proteins are membrane proteins.<ref>Template:Cite journal Template:Open access</ref> Their hydrophobic surfaces make structural and especially functional characterization difficult.<ref name=":1" /><ref>Template:Cite journal</ref> Detergents can be used to render membrane proteins water-soluble, but these can also alter protein structure and function.<ref name=":1" /> Making membrane proteins water-soluble can also be achieved through engineering the protein sequence, replacing selected hydrophobic amino acids with hydrophilic ones, taking great care to maintain secondary structure while revising overall charge.<ref name=":1" />

Affinity chromatography is one of the best solutions for purification of membrane proteins. The polyhistidine-tag is a commonly used tag for membrane protein purification,<ref>Template:Cite journal</ref> and the alternative rho1D4 tag has also been successfully used.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

ReferencesEdit

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External linksEdit

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OrganizationsEdit