Chemokines receptor family

Johnston CJ, Williams JP, Okunieff P, Finkelstein JN. Radiation-induced pulmonary fibrosis examination of chemokine and chemokine receptor families. Radiat Res 2002 157(3) 256-265. 

Chemokine receptors are a family of G protein-coupled receptors that contain seven transmembrane domains. Chemokine receptors are present on the cell surface membrane of leukocytes. As was the case for chemokines, these receptors are also divided into four subgroups CCR is specific for CC chemokines, CXCR for CXC chemokines, XCR1 for C chemokines and CX3CR1 for CX3C chemokines. The CC chemokine receptor family has eleven members, the CXC chemokine receptor family has seven members, and both the C chemokine receptor family and the CX3C chemokine receptor family have one member each. The signal transduction is mediated via the standard G protein-dependent pathway. 

Like ASLV, HIV has a multistep mechanism for activation of membrane fusion. However, low pH is not required for HIV entry, and the virus instead uses a series of distinct interactions with components of the target membrane (reviewed in Dorns and Trono, 2000). The first interaction is with the CD4 protein. This binding event enables a subsequent contact between the HIV SU subunit gpl20 and a molecule of the chemokine receptor family (reviewed in Choe et al, 1998). It is this second interaction with molecules termed coreceptors that activates the membrane fusion potential of the TM subunit gp41 (reviewed in Berger et al, 1999). 

Chemokines exert their action through seven-transmembrane receptors, which are GPCRs (Fig. 4.2). Six CXC receptors, 10 CC receptors, and one receptor each for lymphotactin and fractalkine have been identified. Table 4.1 summarizes the human chemokine receptor family, their ligand specificity, and the cell types that predominantly express these receptors. The new nomenclature for chemokines is also included in the table (8). 

This co-receptor is one or more members of the chemokine receptor family — themselves members of the... 

Horuk, R., 1994. Molecular properties of the chemokine receptor family. Trends Pharmacol. Sci. 15, 159-165. 

Figure 2.3 Multiple sequence alignment of representative members of the chemokine receptor family and the GPCRs with known 3-D structure. The N- and C-terminus are omitted and e2 is only shown from the disulfide-bonded cysteine to TM5. The lengths of the i2 loops of rhodopsin, 3i- and 32-adrenergic receptors and the A2A adenosine receptor are large and they are not shown for clarity. Highly...

The structure of the ligand-free opsin bound to a synthetic peptide derived from the C-terminus of the a-subunit of transducin has recently been obtained [15], This structure has shown that the a5 helix of G t binds to a site in opsin that is opened by the movement of the cytoplasmic end of TM6 away from TM3 and towards TM5 (see above). The C-terminal domain of the G protein interacts with the extended conformation of R3.50, the short loop connecting TM7 and Hx8 and the inner side of the cytoplasmic TMs 5 and 6 (Figure 2.7). Notably, both the G protein family (positions i-2 and i-7 relative to the final amino acid) and TMs 5 (positions 5.61 and 5.65) and 6 (position 6.33) of class A GPCRs contain highly conserved hydrophobic amino adds that form key hydrophobic contacts between the receptor and the G protein. Notably, chemokine receptors also possess hydrophobic amino acids at these 5.61 (I 75% L 10% V 5%), 5.65 (L 90% I 5%) and 6.33 (A 75% L 5%) positions. It, thus, seems reasonable to assume that the mode of recognition of the G protein by the chemokine receptor family resembles this structure found for opsin [15]. 

Graham, G.J. (2009) D6 and the atypical chemokine receptor family novel regulators of immune and inflammatory processes. European Journal of Immunology, 39, 342-351. 

Table 6.1 CXC chemokine receptor family and inflammatory cells.

Chemokine Receptors and Inf ammatory Lung Diseases 115 Table 6.2 CC chemokine receptor family and inflammatory cells. 

CCR3, as well as other members of the chemokine receptor family, are used as coreceptors with CD4 for HIV-1 entry into target cells (83). The recent observations that CCR3 is expressed on microglia in the brain and that eotaxin and an anti-CCR3 antibody effectively inhibit HIV-1 infection of these cells (84) identifies chemokine receptors such as CCR3 as a potential target for anti-HIV therapy. 

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