Integral membrane protein

File:Group 1 and 2 transmembrane protein.png

Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy. They are challenging subjects for study owing to the difficulties associated with extraction and crystallization. In addition, structures of many water-soluble protein domains of IMPs are available in the Protein Data Bank. Their membrane-anchoring α-helices have been removed to facilitate the extraction and crystallization. Search [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/go/?GO=go:0016021 integral membrane proteins] in the PDB (based on gene ontology classification)

IMPs can be divided into two groups:{{cn|date=January 2025}}

1. Integral polytopic proteins (Transmembrane proteins)
2. Integral monotopic proteins

{{Main|Transmembrane protein}}

The most common type of IMP is the transmembrane protein, 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 the membrane several times. Single pass membrane proteins can be categorized as Type I, which are positioned such that their carboxyl-terminus is towards the cytosol, or Type II, which have their amino-terminus towards the cytosol. Type III proteins have multiple transmembrane domains in a single polypeptide, while type IV consists of several different polypeptides assembled together in a channel through the membrane. Type V proteins are anchored to the lipid bilayer through covalently linked lipids. Finally Type VI proteins have both transmembrane domains and lipid anchors.Nelson, D. L., & Cox, M. M. (2008). Principles of Biochemistry (5th ed., p. 377). New York, NY: W.H. Freeman and Company.

Image:Monotopic membrane protein.svg:

1. interaction by an amphipathic α-helix parallel to the membrane plane (in-plane membrane helix)

2. interaction by a hydrophobic loop

3. interaction by a covalently bound membrane lipid (lipidation)

4. electrostatic or ionic interactions with membrane lipids (e.g. through a calcium ion)]]

Integral monotopic proteins are permanently attached to the cell membrane from one side.{{cite journal|last1=Fowler|first1=Philip W.|last2=Coveney|first2=Peter V.|title=A Computational Protocol for the Integration of the Monotopic Protein Prostaglandin H2 Synthase into a Phospholipid Bilayer|journal=Biophysical Journal|date=July 2006|volume=91|issue=2|pages=401–410|doi=10.1529/biophysj.105.077784|pmc=1483072|pmid=16632499|bibcode=2006BpJ....91..401F }}

Three-dimensional structures of the following integral monotopic proteins have been determined:{{cn|date=January 2025}}

• prostaglandin H2 syntheses 1 and 2 (cyclooxygenases)
• lanosterol synthase and squalene-hopene cyclase
• microsomal prostaglandin E synthase
• carnitine O-palmitoyltransferase 2
• Phosphoglycosyl transferase C

There are also structures of integral monotopic domains of transmembrane proteins:{{cn|date=January 2025}}

• monoamine oxidases A and B
• fatty acid amide hydrolase
• mammalian cytochrome P450 oxidases
• corticosteroid 11-beta-dehydrogenases

Many challenges facing the study of integral membrane proteins are attributed to the extraction of those proteins from the phospholipid bilayer. Since integral proteins span the width of the phospholipid bilayer, their extraction involves disrupting the phospholipids surrounding them, without causing any damage that would interrupt the function or structure of the proteins. Several successful methods are available for performing the extraction including the uses of "detergents, low ionic salt (salting out), shearing force, and rapid pressure change".{{Cite journal |last1=Muinao |first1=Thingreila |last2=Pal |first2=Mintu |last3=Boruah |first3=Hari Prasanna Deka |date=2018 |title=Cytosolic and Transmembrane Protein Extraction Methods of Breast and Ovarian Cancer Cells: A Comparative Study |journal=Journal of Biomolecular Techniques|volume=29 |issue=3 |pages=71–78 |doi=10.7171/jbt.18-2903-002 |issn=1524-0215 |pmc=6091320 |pmid=30174558}}

The Protein Structure Initiative (PSI), funded by the U.S. National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health (NIH), 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.{{cite journal |vauthors=Fruchart-Marquer C, Fruchart-Gaillard C, Letellier G, Marcon E, Mourier G, Zinn-Justin S, Ménez A, Servent D, Gilquin B |title=Structural model of ligand-G protein-coupled receptor (GPCR) complex based on experimental double mutant cycle data: MT7 snake toxin bound to dimeric hM1 muscarinic receptor.|journal= J Biol Chem|volume=286|issue=36|pages=31661–75 |date=September 2011 |pmid=21685390 |doi=10.1074/jbc.M111.261404 |pmc=3173127|doi-access=free}}

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.{{cite journal |vauthors=Saier MH, Yen MR, Noto K, Tamang DG, Elkan C |title=The Transporter Classification Database: recent advances |journal=Nucleic Acids Res. |volume=37 |issue=Database issue |pages=D274–8 |date=January 2009 |pmid=19022853 |pmc=2686586 |doi=10.1093/nar/gkn862 |url=}}

As an example of the relationship between the IMP (in this case the bacterial phototrapping pigment, bacteriorhodopsin) and the membrane formed by the phospholipid bilayer is illustrated below. In this case the integral membrane protein spans the phospholipid bilayer seven times. The part of the protein that is embedded in the hydrophobic regions of the bilayer are alpha helical and composed of predominantly hydrophobic amino acids. The C terminal end of the protein is in the cytosol while the N terminal region is in the outside of the cell. A membrane that contains this particular protein is able to function in photosynthesis.{{cite web |url=http://academic.brooklyn.cuny.edu/biology/bio4fv/page/integra.htm |website=academic.brooklyn.cuny.edu |title=Integral membrane proteins |access-date=29 January 2015 |archive-url=https://web.archive.org/web/20150201184055/http://academic.brooklyn.cuny.edu/biology/bio4fv/page/integra.htm |archive-date=1 February 2015 |url-status=dead }}

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
• Glucose Permease
• Ion channels and Gates
• Gap junction Proteins
• G protein coupled receptors (e.g., Beta-adrenergic receptor)
• Seipin
• Photosystem I{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/3333014/ | pmid=3333014 | date=1987 | last1=Golbeck | first1=J. H. | title=Structure, function and organization of the Photosystem I reaction center complex | journal=Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics | volume=895 | issue=3 | pages=167–204 | doi=10.1016/s0304-4173(87)80002-2 }}

• Membrane protein
• Transmembrane protein
• Peripheral membrane protein
• Annular lipid shell
• Hydrophilicity plot
• Inner nuclear membrane protein

{{Reflist|30em}}

{{Cell membranes}}

{{DEFAULTSORT:Integral Membrane Protein}}

*

Category:Protein structure