Chemokine receptors GPCR family

Chemokines exert their biological effects through ceU surface receptors belonging to the family of seven-membrane domain G-protein-coupled receptors (GPCRs, Chen et al. 2004). At least 22 chemokine receptors have been characterized to date, which... 

TM) GPCRs, and the identification of these two molecules facilitated the discovery of many of the other chemokine receptors. The identification of the two IL8 receptors was followed, shortly after, by the cloning of a receptor for CC chemokines. This receptor was initially called CC-CKR1 (now CCR1) and was shown to promiscuously bind a number of members of the CC chemokine family (6). Subsequent to the identification of these three chemokine receptors, two principal methods have been used to clone the cDNAs for the other currently identified receptors ... 

HIV enters the host cell by fusing the lipid membrane of the virus with the host cell membrane. This fusion is triggered by the interaction of proteins on the surface of the HIV envelope with specific cell surface receptors. One of these is CD4, the main receptor for HIV-1 that binds to gpl20, a surface protein on the virus particle.5 CD4 alone, however, is not sufficient to permit HIV fusion and cell entry-an additional co-receptor from the chemokine family of G-protein coupled receptors (GPCRs) is required. The chemokine receptor CCR5 has been demonstrated to be the major co-receptor for the... 

Figure 4.2. Schematic diagram of a two-dimensional model of a chemokine receptor. The extracellular loops (ECL), the putative helical regions that traverse the cell membrane, and the intracellular loops (ICL) are shown. The GPCR (family A) signature disulfide bridge between Cys residues of ECLl and ECL2 is also shown.

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). 

The human chemokine system currently includes more than 40 chemokines and 18 chemokine receptors (Table 1). Chemokine receptors are defined by their ability to induce directional migration of cells toward a gradient of a chemo-tactic cytokine (chemotaxis). Chemokine receptors belong to a family of 7 transmembrane domain, G-protein-coupled cell surface receptors (GPCR) and the ligands are classified into four groups (CXC, CC, C, and CX3Q based on the position of the first two cysteines [1, 2]. Chemokine receptors are present on many different cell types. Initially, these receptors were identified on... 

The viral-encoded GPCRs show highest homology to the family of chemokine receptors. The members of this family can be divided in three subclasses based on their ability to bind to different classes of chemokines. One... 

Chemokines exert their effects by interacting with receptors in the membrane of the target cell, the seven transmembrane-spanning G-protein-coupled receptor (GPCR) (11). As is the case for the chemokines, their receptors can also be grouped into two major families, GGR and GXGR, which interact with the GG and GXG chemokines, respectively (12). 

Chemokine receptors belong to the rhodopsin family of GPCRs [8]. Within this family, the crystal structures have been elucidated for cow rhodopsin (Protein Data Bank accession numbers 1F88, IHZX, IGZM, 1L9H, and 1U19) [9-12] and squid... 

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...

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