Chemokine receptor

Chemokine receptors are proteins on the surface membrane of cells, which bind to chemokines. This binding activates the receptor and triggers a migration of cells, which then move towards the highest chemokine (chemotaxis ). The approximately 20 known chemokine receptors belong to the pharmacologically important group of G protein- coupled receptors. Signal transduction is primarily via heterotrimeric G proteins of the Gi family. Widespread they are in the cells of the immune system that carry several different chemokine receptors in the rule.

Structure and chemokine

Like all G- protein coupled receptors have seven transmembrane regions chemokine receptors, as well as intracellular and three extracellular loops. The binding of the chemokine presumably occurs in two steps: First, the main body of the chemokine binds to the extracellular portion of the receptor, and then 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 triggers its part of a structural change, which also affects the intracellular portion of the receptor. Therefore exists between chemokine receptor and a number of binding sites, and only as complete as possible binding triggers the activation of the receptor from.

Nomenclature

The nomenclature of chemokine receptors is derived from the family membership of the binding partners. Chemokines can be assigned to four different families and each receptor binds exclusively to members of a particular chemokine. The name of the receptor is now composed of a short description of the chemokine (CC, CXC, CX3C, or XC), an R for receptor and a consecutive numbering. It can thus, for example, CCR1 or CXCR2 loud.

Pathology

Variants of CCR2 and CCR5 genes are responsible for hereditary immunity against infection with the HIV virus. CCR5 mutations may also cause hereditary diabetes mellitus and susceptibility to infection with the West Nile virus.

Mutations in the CXCR4 gene are responsible for WHIM syndrome. A CXCR6 variant, which is common in Africa, increases the survival time significantly in infection with HIV and Pneumocystis carinii pneumonia. Another variation in CXCR1 protects against rapid development of AIDS. Mutations in CX3CR1 may be reduced risk of coronary heart disease, but also an increased risk of age-related macular degeneration ( AMD) and rapid progress in AIDS cause.