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.
Three-dimensional structures of only ~160 different integral membrane proteins are currently determined at atomic resolution by gene ontology classification)
IMPs can be divided into two groups:
Integral Polytopic Protein
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
Integral monotopic proteins, are associated to the membrane from one side but do not span the lipid bilayer completely.
Determination of Protein Structure
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.
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.
Examples of integral membrane proteins:
- Insulin receptor
- Some types of cell adhesion proteins or cell adhesion molecules (CAMs) such as Integrins, Cadherins, NCAMs, or Selectins.
- Some types of receptor proteins
- Band 3
- Membrane proteins
- Transmembrane proteins
- Peripheral membrane proteins
- Orientations of Proteins in Membranes database
- Hydrophilicity plots
- Inner nuclear membrane proteins
- The Human Membrane Proteome - A comprehensive article covering the transmembrane protein component of the human proteome
- Membrane PDB Database of 3D structures of integral membrane proteins and hydrophobic peptides with emphasis on crystallization conditions
- Membrane proteins of known 3D structure from Stephen White laboratory