Membrane proteins constitute one of the three main protein classes, with the other classes being the fibrous and globular proteins. Membrane proteins are attached to, or associated with the membrane of a cell or an organelle. These proteins are specifically targeted to different types of biological membranes.  They are also the target of over 50% of all modern medicinal drugs. It is estimated that 20-30% of all genes in most genomes encode membrane proteins.
Membrane proteins perform a variety of functions vital to the survival of organisms:
- 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 categorised according to the Transporter Classification database.
- Membrane enzymes for example Oxidoreductases, Transferases and Hydrolases.
- Cell adhesion molecules allowed cells to identify each other and interact. For example proteins involved in immune response.
A slightly different classification is to divide all membrane proteins to integral and amphitropic. The amphitropic are proteins that can exist in two alternative states: a water-soluble and a lipid bilayer-bound. The amphitropic protein category includes water-soluble channel-forming polypeptide toxins, which associate irreversibly with membranes, but excludes peripheral proteins that interact with other membrane proteins rather than with lipid bilayer.
Integral membrane proteins
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. They can be classified according to their relationship with the bilayer:
- Integral polytopic proteins, also known as "transmembrane proteins," are integral membrane proteins which span across the membrane at least once. They have one of two tertiary structures:
- Integral monotopic proteins are integral membrane proteins which are attached to only one side of the membrane and do not span the whole way across.
Peripheral membrane proteins
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.
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 aggregate and associate irreversibly with the lipid bilayer and become reversibly or irreversibly membrane-associated.
The most common tertiary structures are Helix bundle and Beta barrel. The portion of the membrane proteins that are attached to the lipid bilayer are consisting of hydrophobic amino acids only. This is done so that the peptide bonds' carbonyl and amine will react with each other instead of the hydrophobic surrounding. The portion of the protein that is not touching the lipid bilayer and is protruding out of the cell membrane are usually hydrophilic amino acids.
Membrane proteins have hydrophobic surfaces, are relatively flexible and are expressed at relatively low levels. This creates difficulties in obtaining enough protein and then growing crystals. Hence despite the significant functional importance of membrane proteins, determining atomic resolution structures for these proteins is more difficult than globular proteins. As of January 2013 less than 0.1% of protein structures determined were membrane proteins despite being 20-30% of the total proteome.
Many of the successful membrane protein structures are characterized by X-ray crystallography and are very large structures in which the interactions with the membrane mimetic environments can be anticipated to be small in comparison to those within the protein structures. The small domains are particularly sensitive to the influence of membrane mimetic environments, potentially leading to non-native structures. Fortunately, there are many sample preparation conditions that can be chosen for crystallization and for solution NMR. All membrane protein structural biology should be subjected to careful scrutiny; through a combination of structural methodologies it should be possible to achieve an understanding of the native functional state for membrane protein structures. Coevolution information has been successfully exploited for prediction of multiple large (membrane) protein structures.
- Integral membrane proteins
- Transmembrane proteins
- Peripheral membrane proteins
- Ion pump (biology)
- Carrier protein
- Ion channel
- Receptor (biochemistry) (including G protein-coupled receptor)
- List of MeSH codes (D12.776)
- Inner nuclear membrane proteins
White, Stephen. “General Principle of Membrane Protein Folding and Stability.” Stephen White Laboratory Homepage. 10 Nov. 2009. web.
- Classification of membrane proteins with known 3D structure to different membrane types
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- Membrane Proteins of known 3D Structure
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- State of the art in membrane protein prediction
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- Membrane Protein Structural Dynamics Consortium
- Transmembrane Protein Center at University of Wisconsin-Madison
Membrane protein databases
- List of transmembrane proteins of known 3D structure
- TCDB - Transporter Classification database
- Orientations of Proteins in Membranes (OPM) database 3D structures of integral and peripheral membrane proteins arranged in the lipid bilayer
- Membrane PDB Database of 3D structures of integral membrane proteins and hydrophobic peptides with an emphasis on crystallization conditions
- Protein Data Bank of Transmembrane Proteins 3D models of all transmembrane proteins currently in PDB. Approximate positions of membrane boundary planes were calculated for each PDB entry.
- TransportDB Genomics-oriented database of transporters from TIGR
- Membrane targeting domains (MeTaDoR)
- The Human Membrane Proteome - A comprehensive article covering the transmembrane protein component of the human proteome