Membrane proteins are proteins that interact with, or are part of, biological membranes. They include integral membrane proteins that are permanently anchored or part of the membrane and peripheral membrane proteins that are only temporarily attached to the lipid bilayer or to other integral proteins. The integral membrane proteins are classified as transmembrane proteins that span across the membrane and integral monotopic proteins that are attached to only one side of the membrane. Membrane proteins are a common type of proteins along with soluble globular proteins, fibrous proteins, and disordered proteins. They are targets of over 50% of all modern medicinal drugs. It is estimated that 20–30% of all genes in most genomes encode membrane proteins.
Compared to other classes of proteins, the determination of membrane protein structures has remained a challenge in large part due to the difficulty in establishing experimental conditions where the correct conformation of the protein in isolation from its native environment is preserved.
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 categorized according to the Transporter Classification database.
- Membrane enzymes may have many activities, such as oxidoreductase, transferase or hydrolase.
- Cell adhesion molecules allow cells to identify each other and interact. For example, proteins involved in immune response.
Integral membrane proteinsEdit
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. One such example of this type of protein which has not been functionally characterized yet is SMIM23. 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. These proteins have one of two structural architectures:
- 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.
- 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
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.
Integral and peripheral proteins may be post-translationally modified, with added fatty acid, diacylglycerol or prenyl chains, or GPI (glycosylphosphatidylinositol), which may be anchored in the lipid bilayer.
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.
A large fraction of all proteins are thought to be membrane proteins. For instance, about 1000 of the ~4200 proteins of E. coli are thought to be membrane proteins. The membrane localization has been confirmed for more than 600 of them experimentally. The localization of proteins in membranes can be predicted very reliably using hydrophobicity analyses of protein sequences, i.e. the localization of hydrophobic amino acid sequences.
Purification of membrane proteinsEdit
The activity of membrane proteins decrease very fast in contrast to other proteins. Affinity chromatography provides a fast and specific purification of membrane proteins. The polyhistidin-tag is the common used tag for protein purification.
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Membrane protein databasesEdit
- TCDB - Transporter Classification database, a comprehensive classification of transmembrane transporter proteins
- Orientations of Proteins in Membranes (OPM) database 3D structures of integral and peripheral membrane proteins arranged in the lipid bilayer
- Protein Data Bank of Transmembrane Proteins 3D models of transmembrane proteins approximately arranged in the lipid bilayer.
- TransportDB Genomics-oriented database of transporters from TIGR
- Membrane PDB Database of 3D structures of integral membrane proteins and hydrophobic peptides with an emphasis on crystallization conditions
- Mpstruc database - A curated list of selected transmembrane proteins from the Protein Data Bank
- MemProtMD a database of membrane protein structures simulated by coarse-grained molecular dynamics
- Membranome database provides information about bitopic proteins from several model organisms