Chemokine receptors
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Chemokine receptors are proteins in the surface membrane of cells that bind to chemokines . This binding activates the receptor and triggers a migration of the cells, which then move in the direction of the highest chemokine concentration ( chemotaxis ). The approximately 20 known chemokine receptors belong to the pharmacologically important group of G-protein-coupled receptors . The signal transduction takes place primarily via heterotrimeric G proteins of the G i family. They are widespread in the cells of the immune system , which usually carry several different chemokine receptors.
Structure and chemokine binding
Like all G-protein-coupled receptors, chemokine receptors have seven transmembrane areas and three intracellular and three extracellular loops. The chemokine is likely to bind in two steps: First, the main body of the chemokine binds to the extracellular part of the receptor, whereupon the flexible amino terminus of the chemokine changes its spatial structure. In the second step, the amino terminus binds to binding sites within the transmembrane domains of the chemokine receptor and in turn triggers a structural change that also affects the intracellular part of the receptor. There is therefore a large number of binding sites between the receptor and the chemokine, and only the most complete possible binding triggers activation of the receptor.
nomenclature
The nomenclature of the chemokine receptors is derived from the family membership of the attachment partner. Chemokines can be assigned to four different families and each receptor only binds to members of a specific chemokine family. The name of the receptor is now made up of the abbreviation of the chemokine family (CC, CXC, CX3C or XC), an R for receptor and consecutive numbering. For example, it can be CCR1 or CXCR2. An exception to this system is the chemokine receptor DARC , which is not capable of classic signal transmission and is therefore different from the other receptors .
| Surname | Alternative names | Endogenous ligands |
|---|---|---|
| CCR1 | CD191 | CCL3 , CCL5 , CCL7 , CCL8 , CCL13, CCL14, CCL15, CCL16, CCL23 |
| CCR2 | CD192 | CCL2 , CCL7, CCL8, CCL13 |
| CCR3 | CD193 | CCl5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL24, CCL26 |
| CCR4 | CD194 | CCL17, CCL22 |
| CCR5 | CD195 | CCL3, CCL4, CCL5, CCL8, CCL14 |
| CCR6 | CCL20 | |
| CCR7 | BLR2, EBI1 | CCL19, CCL21 |
| CCR8 | CCL1, CCL4, CCL17 | |
| CCR9 | CCL25 | |
| CCR10 | CCL26, CCL27, CCL28 | |
| CXCR1 | CD181, CD128a, IL-8Ra | CXCL6, CXCL8 |
| CXCR2 | CD182, CD128b, IL-8Rb | CXCL1 , CXCL2, CXCL3, CXCL5, CXCL7, CXCL8 |
| CXCR3 | CD183 | CXCL9 , CXCL10, CXCL11 |
| CXCR4 | CD184, Fusin, LESTR | CXCL12 |
| CXCR5 | CD185, BLR1 | CXCL13 |
| CXCR6 | BONZO, TYMSTR | CXCL16 |
| CXCR7 | RDC1 | CXCL11, CXCL12 |
| CX 3 CR1 | CX3CL1 | |
| XCR1 | XCL1, XCL2 | |
| DARC | CD234, Duffy antigen | CXCL1, CXCL7, CXCL8, CCL2, CCL5 |
pathology
Variants of the genes CCR2 and CCR5 are responsible for hereditary immunity to infection with the HI virus. CCR5 mutations can also lead to hereditary diabetes mellitus and susceptibility to infection with West Nile virus .
Mutations in the CXCR4 gene are the cause of the WHIM syndrome . A variant of CXCR6 , which is common in Africa, significantly increases survival time when infected with HIV and Pneumocystis carinii pneumonia. Another variant in CXCR1 protects against the rapid progression of the AIDS disease. Mutations in CX3CR1 can lead to a reduced risk of coronary artery disease , but also an increased risk of age-related macular degeneration (AMD) and a rapid course of AIDS.
literature
- Charles A. Janeway, Paul Travers, Mark Walport: Immunobiology . B&T; 6th edition (2005) ISBN 0-8153-4101-6
- SJ Allen et al .: Chemokine: receptor structure, interactions, and antagonism. In: Annu. Rev. Immunol. Vol. 25, 2007, pp. 787-820. PMID 17291188
swell
- ↑ EJ Fernandez et al .: Structure, function, and inhibition of chemokines. In: Annu. Rev. Pharmacol. Toxicol. Vol. 42, 2002, pp. 469-499. PMID 11807180 .
- ^ PM Murphy et al .: International union of pharmacology. XXII. Nomenclature for chemokine receptors. In: Pharmacol. Rev. Vol. 52, No. 1, 2000, pp. 145-176. PMID 10699158 .
- ↑ 609423. In: Online Mendelian Inheritance in Man . (English), 612522. In: Online Mendelian Inheritance in Man . (English), 610379. In: Online Mendelian Inheritance in Man . (English).
- ↑ 605163. In: Online Mendelian Inheritance in Man . (English), 146929. In: Online Mendelian Inheritance in Man . (English), 601470. In: Online Mendelian Inheritance in Man . (English).