Integral membrane protein

An Integral Membrane Protein (IMP) is a protein molecule (or assembly of proteins) that in most cases spans the biological membrane with which it is associated (especially the plasma membrane) or which, in any case, is sufficiently embedded in the membrane to remain with it during the initial steps of biochemical purification (compare peripheral membrane protein).

Cells assemble IMPs in the endoplasmic reticulum. A short signal sequence at the N-terminus typically marks a protein as destined for installation in the membrane.

IMPs rarely diffuse freely within the membrane but rather most are anchored to the cytoskeleton.

IMPs comprise a very significant fraction of the proteins encoded in the genome.

Structure
There are many types of IMPs with wildly different structures. Although the structures of thousands of proteins have become known by X-ray diffraction and nuclear magnetic resonance spectroscopy, the structures of only a few dozen integral membrane proteins are known at atomic resolution, because they tend to denature on removal from the membrane, under which condition they are impossible to analyze. Without removing them from the membrane, it is difficult to form the 3-dimensional crystals required for X-ray crystallography. This difficulty spurred the development of electron crystallography, which can determine protein structures from 2-dimensional arrays or helices. Solution structural studies of membrane proteins by Nuclear magnetic resonance Spectroscopy have traditionally been limited by technical and practical difficulties. High-yield expression, purification, refolding or extraction of membrane proteins in appropriate detergent micelle for structural studies and faster relaxation of signal due to the large size of membrane protein-micelle complex pose much more challenges than the corresponding work with soluble proteins. Preparation of perdeutrated membrane proteins and modern solution NMR techniques now enable studies of these larger structures through the application of the principles of transverse relaxation-optimized spectroscopy (TROSY). However, only a few efforts in this vein have attained atomic resolution, and X-ray crystallography remains the dominant method of IMP structure determination.

In general, IMPs can be divided into three groups:
 * 1) Transmembrane
 * 2) Membrane-associated
 * 3) Lipid-linked

Transmembrane
A transmembrane IMP is an integral membrane protein that spans from the internal to the external surface of the biological membrane or lipid bilayer in which it is embedded. This is the most common type of IMP.

A hydrophobic domain of the protein resides in the oily core of the membrane, while hydrophilic domains protrude into the watery environment inside and outside the cell or compartment. Transmembrane proteins often have their N-terminal on the exoplasmic face and their C-terminal on the cytoplasmic face. Many transmembrane proteins have multiple membrane-spanning alpha helix segments which anchors them to the membrane. Most transmembrane proteins have an internal topogenic sequence.

There are two basic types of transmembrane proteins:
 * 1) Single-pass
 * 2) Multi-pass transmembrane proteins have that multiple topogenic sequences.

Membrane-associated
A membrane-associated IMP is located entirely in the cytosol, and is attached to the cytosolic layer of the membrane with an amphipathic α helix.

Lipid-linked
Lipid-Linked IMPs are located entirely outside the bilayer, on either inside or outside of the cell, and are connected to the bilayer with one or more covalently attached lipid groups.

Function
Most commonly, the function of IMPs is to act as a transporter for various molecules that would, otherwise, not be able to move across a cell membrane. When used as a transporter, its most common configuration is to have an extra-cellular domain and a cytoplasmic domain separated by a non-polar region that holds it tightly in the cell membrane.

Examples of the other functions that integral membrane proteins serve include the identification of a cell for recognition by other cells, the anchoring of one cell to another or to surrounding media, and the initiation of intracellular responses to external molecules. IMPs can be receptors, channels or enzymes.

Types
Following is a list of types of integral membrane proteins:
 * Integrin
 * Cadherin
 * Insulin receptor
 * NCAM
 * Selectin
 * Some types of cell adhesion proteins
 * some types of receptor proteins
 * Glycophorin

بروتين غشائي مدمج Integraalinen kalvoproteiini