Chemokine transmembrane domain

Chemokines are a superfamily of low-molecular-weight chemotactic cytokines that exert their effects through seven transmembrane domain G protein-coupled receptors. Although some chemokines are constitutively expressed in certain settings, most are induced by proinflammatory mediators, such as IFN-y and TNF-a. Upon binding to the appropriate receptor, chemokines initiate a... 

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. 

Figure 4.5. Top view of a chemokine binding site model (a), showing only the helical backbone of residues in transmembrane domains I-VII the side chain for the conserved Glu in TM (VII) is shown. Top view of a biogenic amine binding site model (b), showing only the helical backbone of residues in transmembrane domains 1-VII the side chain for the conserved Asp residue in TM (III) is shown.

Table 2 Chemokine-binding proteins with seven transmembrane domain motif, not yet demonstrated to signal...

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... 

As mentioned earlier, the biological activities of chemokines are mediated by distinct members of the rhodopsin-like seven-transmembrane domain, G-protein-coupled receptor superfamily [65], Other receptors exist that bind chemokines with high affinity and specificity [16]. However, these receptors are structurally incapable of transducing signals and are therefore designated as decoy receptors. 

Chemokines bind to seven transmembrane domain proteins coupled to GTP-binding proteins with homology to the family of chemotactic receptors. Five receptors for C-X-C chemokines (CXCRl to 5) and nine for C-C chemokines (CCRl to 9) were recently cloned (Table 1). These receptors show a promiscuous pattern of ligand recognition and are differentially expressed and regulated in leukocytes (Baggiolini et al., 1997 Izumi et al., 1997 Nibbs et al., 1997 Rollins, 1997 Legler et al., 1998). The... 

CC chemokine activities are mediated by seven-transmembrane domain, Gprotein-coupled receptors (see Chap. 2). The CC chemokine receptors are structurally homologous. While the transmembrane and the second and third intracellular/ cytoplasmic domains of these receptors are well conserved, the NH2- and COOH-... 

Viral seven-transmembrane-domain chemokine receptor vCKR... 

Chemokines, c/jemoattractant cytokines, are small (8—14 kDa) proteins that bind to G-protein-coupled receptors composed of seven transmembrane domains (BaggioHni, 1998). The chemokine family encompasses more than 50 members, which can be either homeostatic or inflammatory (Zlotnik Yoshie, 2000). The former are constitutively expressed in certain tissues and have roles in tissue development, such as angiogenesis or neovascularization, or basal leukocyte migration (Rot von Andrian, 2004). In the latter, an infection or other proinflammatory stimulus (TNF-a) will cause the release of chemokines that will direct the recruitment of leukocytes (e.g., neutrophils, monocytes, etc.) toward the site of inflammation (Zlotnik, Burkhardt, Homey, 2011). 

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