An Integral Membrane Protein (IMP) is a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane. Such proteins can be separated from the biological membranes only using detergents, nonpolar solvents, or sometimes denaturing agents.

IMPs comprise a very significant fraction^{[citation needed]} of the proteins encoded in an organism's genome.

Contents 1 Structure 1.1 Integral transmembrane protein 1.2 Integral monotopic proteins 2 Function 3 Examples 4 See also 5 References 6 External links

[edit] Structure

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:

1. Transmembrane proteins
2. Integral monotopic proteins

[edit] Integral transmembrane 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. TM proteins can be categorized as Type I, which are positioned such that their amino-terminus is outside of the membrane, or Type II, which have their carboxy-terminus outside of the membrane.

[edit] Integral monotopic proteins

Integral monotopic proteins, are permanently attached to the membrane from one side.

Three-dimensional structures of the following integral monotopic proteins have been determined:

• prostaglandin H2 syntheses 1 and 2 (cyclooxygenases) [1],
• lanosterol synthase and squalene-hopene cyclase [2],
• microsomal prostaglandin E synthase [3],
• carnitine O-palmitoyltransferase 2 [4].

There are also structures of integral monotopic domains of transmembrane proteins:

• monoamine oxidases A and B [5],
• fatty acid amide hydrolase [6],
• mammalian cytochrome P450 oxidases [7],
• corticosteroid 11-beta-dehydrogenases [8].

Such domains require detergents for extraction or crystallization, even after removal of their transmembrane helices. Therefore, they are often classified as integral monotopic proteins [9]

[edit] Function

IMPs include transporters, 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 TCDB database.

[edit] Examples

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
• Glycophorin
• Rhodopsin
• Band 3
• CD36

[edit] See also

• Membrane proteins
• Transmembrane proteins
• Peripheral membrane proteins

[edit] References

• Booth, P.J., Templer, R.H., Meijberg, W., Allen, S.J., Curran, A.R., and Lorch, M. 2001. In vitro studies of membrane protein folding. Crit. Rev. Biochem. Mol. Biol. 36: 501-603.
• Bracey M.H., Cravatt B.F., Stevens R.C., Cravatt B.F. 2004. Structural commonalities among integral membrane enzymes. FEBS Lett. 567: 159-165.
• Bowie J.U. 2001. Stabilizing membrane proteins. Curr. Op. Struct. Biol. 11: 397-402.
• Bowie J.U. 2005. Solving the membrane protein folding problem. Nature 438: 581-589.
• DeGrado W.F., Gratkowski H. and Lear J.D. 2003. How do helix-helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo-oligomeric helical bundles. Protein Sci. 12: 647-665.
• Popot J-L. and Engelman D.M. 2000. Helical membrane protein folding, stability, and evolution. Annu. Rev. Biochem. 69: 881-922.
• Protein-lipid interactions (Ed. L.K. Tamm) Wiley, 2005.

[edit] External links

• 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
• Orientations of proteins in membranes database Calculated spatial positions of transmembrane, integral monotopic, and peripheral proteins in membranes

v • d • e Protein: membrane proteins / membrane glycoproteins / integral membrane proteins Transmembrane protein Transmembrane receptors (CD33) Peripheral membrane protein Lipid anchored protein Pore-forming toxin antimicrobial cationic peptide (Cathelicidin, Cecropin, Defensin, Dermcidin, Histatin, Magainin, Melitten, Polymyxin, Thionin) · Bacteriocin · Gramicidin (Gramicidin S) · Hemolysin · Leukocidin · Perforin · Streptolysin Transfer/transport Membrane transport proteins · Phospholipid transfer proteins · Vesicular transport proteins Cytoskeleton Ankyrin · Dystrophin · Spectrin · Utrophin Ungrouped Arrestin · Calnexin · Connexin · Ephrin · Heterotrimeric GTP-binding proteins · LDL-receptor-related protein associated protein · Membrane fusion protein (VAMP) · Myelin basic protein · Neurofibromin 2 · Presenilin (PSEN1, PSEN2) · Protoporphyrinogen oxidase · pulmonary surfactant (Pulmonary surfactant-associated protein B, Pulmonary surfactant-associated protein C) · Tetraspanin · Peroxin