Cysteine chemokine receptors

Cysteine-cysteine chemokine receptor 5 (CCR5) A 32-bp deletion with a population frequency of about 0.1 in Caucasians results in truncated nonfunctional receptor. Carriers of this variant are partially protected from HIV infection, particularly the homozygous carriers. 

T-cells, representing the adaptive arm of the immune response, also play a critical role in atherogenesis, and enter lesions in response to the chemokines inducible protein-10 (DP-10), monokine induced by DFN-y (MIG), and DFN-inducible T-cell a-chemoattractant (I-TAC), which bind CXCR3 (a chemokine receptor containing two cysteine residues separated by one amino acid), highly expressed by T lymphocytes in the plaque. The... 

The organization of chemokine families based on the cysteine sequence has functional significance. Some human chemokines can compete for binding and activation of receptors with other intrafamily chemokines. This raised the possibility that significant structural differences in chemokine-receptor interactions... 

Data from studies with other GPCRs have highlighted the importance of extracellular cysteines in ligand binding and the maintenance of the conformational integrity of the receptors. There are typically four conserved cysteine residues found on extracellular domains of chemokine receptors (see Figure 1 and Tables 2 and 3) one on the amino-terminus and one on each of the three extracellular loops. It is clear that the cysteines on extracellular loops 1 and 2 form a disulfide bond that is essential for the proper trafficking of the receptors... 

A further importance of cysteines lies in the palmitoylation of chemokine receptors. Many chemokine receptors have cysteine residues in their carboxy-terminal regions. In other GPCRs, these have been implicated in palmitoylation and in the anchoring of the carboxy-terminus to the plasma membrane. This effectively generates a fourth intracellular loop in the receptors. Studies on CCR5 have identified a three-cysteine cluster in the carboxy-terminus that is... 

Clustering of a certain number of CD4 and coreceptor molecules is presumed to be necessary for the efficient HIV-1 Env-mediated fusion pore formation. It has been proposed that four to six CCR5 molecules (91) and three CD4 binding events are needed to induce fusion between the viral and host cell membranes (92). Both CD4 (93) and chemokine receptors can form functional dimers (94) in the plasma membrane. It was proposed that formation of CD4 dimers, mediated by a disulfide bond between the cysteine residues of the D2 domain, might enhance HIV-1 entry and infection (95,96). In contrast, others have provided... 

CTAC CTES CV CVD cw CXCR4 cetyltrimethylammonium chloride carboxyethylsilanetriol, sodium salt cyclic voltammetry chemical vapor deposition continuous wave CXC chemokine receptor CXC stands for a C-X-C motif with C = cysteine and X = arbitrary amino acid... 

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 chemokines are a family of cytokines with low molecular weights that predominately regulate the trafficking of leukocytes. There are currently 40 known chemokines and 16 chemokine receptors, with the majority of the chemokines binding to more than one receptor [10, 11]. The chemokine family can be subdivided into four groups based on the location of the first two cysteines C, C-C, C-X-C and C-X3-C. Five C-X-C chemokine receptors and 11 C-C chemokine receptors have been identified to date [11]. Interaction of chemokines with their receptors on PMN not only induces directional migration but also activates PMN adhesion, degranulation and surface marker expression. 

Chemokines are divided into four subclasses CXC, CC, CX3C, and C, based on the number and spacing of conserved cysteines. Because many chemokines can bind more than one receptor, and many chemokine receptors can bind more than one chemokine, but not from more than one subclass, a systematic nomenclature has been devised in which each receptor name contains an appropriate chemokine subclass root followed by the letter R, denoting receptor, and a unique number (2). Recently, a decade-long chaos in chemokine ligand nomenclature has been brought to order by a standardized system that uses the same subclass and unique number rule established first for the receptors (3). 

Until recently, the structural subclassification based on the arrangement of the cysteine motif was an adequate classification system for chemokines and their receptors. However, this classification based on structure did not provide any indication of the functional role of the various chemokines. Therefore, an alternative system that relates expression to function has recently been developed. In this system, chemokines and chemokine receptors are classified according to their functional expression as either homeostatic/constitutive or inflamma-tory/inducible (Fig. 2). Homeostatic chemokines are expressed constitutively within lymphoid tissues and regulate movement of thymocytes through the thymus during selection and... 

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