Chemokines four families

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. 

Another remarkable aspect of this protein is its ability to bind many different chemokines across all four families with nanomolar affinities (van Berkel et al, 2000). While no common chemokine sequence motifs have been identified thus far, the promiscuity of M3 has been partly attributed to structural plasticity as a consequence of its oligomeric framework, which can undergo structural rearrangements, and the use of flexible loops as primary contact regions. Future studies of additional M3 chemokine complexes will undoubtedly provide further insight into the brilliant design of this highly evolved viral stealth weapon. 

Chemokines, a sub-family of the cytokines. They are composed of a core domain containing two or three disulfide bonds in a flexible N-terminal domain whose truncation affects the potency of receptor activation. The chemokines are homologous 8- to 10-kDa proteins with 20 to 70% sequence homology. They are subdivided into at least four families based on the relative position of the Cys residues in the mature protein, although only the a- and -chemokines (both of which contain four Cys residues) have been well characterized. In the a-chemokines (CXC chemokines), the first two Cys residues are separated by a single amino acid residue (Cys-Xaa-Cys), whereas in the -chemokines (CC chemokines) the first two Cys residues are adjacent to each other (Cys-Cys). a-Chemokines are roughly 70 to 130 aa in size and are secreted with leader sequences of 20-25 aa which are cleaved before release. Besides the conserved Cys-Xaa-Cys motif near the N-terminus of the protein. 

Structural criteria originally led to the classification of the nearly 50 known chemokines in four families, C, CC, CXC, and CX3C. Today scientists refer to them as constitutive chemokines, which are usually regulated during development, and as inducible chemokines, whose expression is regulated mainly during inflammatory processes. 

Chemokines are a family of small cytokines, or proteins secreted by cells. Proteins are classified as chemokines according to shared structural characteristics such as small size (8-10 kDa in size), and the presence of four... 

Chemokines are the largest family of cytokines. Four invariant cysteines define the chemokine proteins. They are grouped on the basis of the conservation of the domain containing the first two cysteines. 

One of the interesting questions is why this approach has not been reported to have been used to successfully identify new members of other families of cytokines, such as the four helix bundle family which includes IL-2, IL-4, IL-5, etc. One problem for these families is that the defining features are not so apparent (for example the positions of the disulfide bonds are not always conserved). Also, the majority of the members of these cytokine families are only finally confirmed once their three-dimensional structures have been solved. It may be that when more sophisticated versions of such techniques as Profile searching can be used will this then open up new cytokines for more classical families. Such Profiles would have to include amino acid similarities, as well as secondary structure propensity. Even so, the current rate of success is not expected to be as high as for the chemokine area (see, for example, ref. 15). 

Only the primary sequence of MDC is known. MDC is a member of the CC family of chemokines and shares 28-35% amino acid identity with this group of proteins. This sequence conservation includes the four characteristic cysteines and nine other highly conserved residues (Chang et al., 1997 Godiska et al, 1997). At the C-terminus of MDC there is a stretch of basic residues which is also conserved within the chemokine family and which mediates their ability to interact with heparin. 

Chemokines are a family of small (8-lOkDa) protein cytokines, with four cysteine residues in conserved locations that are key to forming their three-dimensional shape. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells they are c/temotactic cytokines. 

Human MCP-1 (Fig.l) is a protein of 76 amino acids (MW 8.6 Kd). It contains four cysteines at positions 11, 12, 36 and 52, which are present as two disulfide bonds in the native form (3,4). MCP-1 belongs to a family of proteins, called CC chemokines since they contain adjacent cysteine residues at positions 11 and 12 (5,6). It is also related to another family of chemokines, referred to as the CXC family of chemokines in which the first two cysteine residues are separated by a single amino acid residue(5, 6). The disulfide bonding pattern of MCP-1 has not been determined. The disulfide bonds as shown in Figure 1 have been deduced (3), based on the disulfide bonding pattern determined for the CXC chemokines p-thyroglobulin (7) and IL-8 (8). 

Chemokines (alternatively known as intercrines, PF-4 superfamily of cytokines or SIS cytokines) are members of a superfemily of small (8-10 kDa), inducible, secreted, pro-inflammatory cytokines. The sequences of members of the chemokinc family have a conserved four-cysteine motif, and are divided into two branches with the first two cysteines separated by another amino acid residue (C-X-C), or the first two cysteines are adjacent (C-C) (Oppenheim et al., 1991). The C-X-C chemokines include IL-8, /3-thromboglobulin (/3-TG) and platelet factor 4 (PF4), and the C-C chemokines include MIP-la, MIP-I18, RANTES, MCP-l/MCAF, MCP-2 and MCP-3. 

Chemokine family. The mediators are divided into four subclasses according to chemical characteristics of the ligands, namely the number or positions of cyteine residues, as follows CC chemokines CXC chemokines CX3C chemokine C chemokines. These chemokines act at receptors largely named after the peptides themselves, and include CCCRl-8 and CXRl-4. (Chemokines recognized include MIP-la MIP-ip MCP-1 MCP-2 MCP-3 MCP-4 MIP-5 RANTES LCRl leukotactin-1 eotaxin, eotaxin-1 and some other chemokines. 

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... 

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