An integral membrane protein (IMP) is a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can be separated from the biological membranes only using detergents, nonpolar solvents, or sometimes denaturing agents.
IMPs comprise a very significant fraction of the proteins encoded in an organism's genome.[1]
All transmembrane proteins are IMPs, but not all IMPs are transmembrane proteins.[2]
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Three-dimensional structures of only ~160 different integral membrane proteins are currently determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy due to the difficulties with extraction and crystallization. In addition, structures of many water-soluble domains of IMPs are available in the Protein Data Bank. Their membrane-anchoring α-helices have been removed to facilitate the extraction and crystallization.
IMPs can be divided into two groups:
The most common type of IMP is the transmembrane protein (TM), which spans the entire biological membrane. Single-pass membrane proteins cross the membrane only once, while multi-pass membrane proteins weave in and out, crossing several times. Single pass TM proteins can be categorized as Type I, which are positioned such that their carboxy-terminus is towards the cytosol, or Type II, which have their amino-terminus towards the cytosol.
Integral monotopic proteins, are permanently attached to the membrane from one side. Such domains require detergents for extraction or crystallization, even after removal of their transmembrane helices. Therefore, they are often classified as integral monotopic proteins[3]
The Protein Structure Initiative (PSI), funded by the U.S. National Institute of General Medical Sciences (NIGMS), has among its aim to determine three-dimensional protein structures and to develop techniques for use in structural biology, including for membrane proteins. Homology modeling can be used to construct an atomic-resolution model of the "target" integral protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous protein. This procedure has been extensively used for ligand-G protein-coupled receptors (GPCR) and their complexes.[4]
IMPs include transporters, linkers, channels, receptors, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction of energy, and proteins responsible for cell adhesion. Classification of transporters can be found in Transporter Classification database.[5]
Examples of integral membrane proteins:
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