Chemoattractant protein-1, amino acid

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... 

Figure 1. Amino acid sequence of human Monocyte Chemoattractant Protein-1 (2,3).

Beall, C. J., Mahajan, S., and Kolattukudy, P. E. (1992). Conversion of monocyte chemoattractant protein-1 into a neutrophil attractant by substitution of two amino acids. J. Biol. Chem. 267, 2455-2459. 

The chemokines are a family of small (8-12kDa) secreted chemoattractant cytokines that share a common structure dictated by the pattern of disulfide bonds that form between conserved cysteine (C) residues. The number and spacing of cysteines in the amino-terminus defines four chemokine classes, CXC, CC, XC and CX3C, where X represents any amino acid (aa) except C (Baggiolini and Loetscher 2000). A majority of chemokines have two sets of disulfide bonds formed by the pairing the first two cysteines (Ci and C2) with two others in a C1-C3 and C2-C4 pattern. These secreted proteins bind to G protein-coupled heptahelical receptors found on leukocytes that are designated by the class of chemokine bound (CXCRs, CCRs, XCRs, and CX3CR, respectively) (Rossi and Zlotnik 2000). 

The first diemokine, PF-4, was identified in 1977 [3] but it was not for almost a decade that other members of the family started to emerge, with the discovery of the proinflammatory chemokines IP-10 was identified in 1985 as a protein showing homology to PF4 [4], while IL-8 and the MI P-1 proteins were isolated in the late 1980s as active protein from tissues or culture supernatants. The neutrophil chemoattractant, IL-8, was purified from culture supernatant of stimulated blood monocytes [5] and the monocyte chemoattractants MIP-la and MIP-ip were purified from LPS-stimulated mouse macrophages [6]. The primary amino acid sequence of these chemokines rapidly led to the identification of the highly conserved four-cysteine motif described above and also allowed their classification into the two principal subclasses. The number of chemokines then grew rapidly... 

All of the CXC ligand proteins are active as chemoattractant factors. As mentioned earlier, the first chemokine identified was CXCLS, which has now been extensively characterized and will thus be used as a representative for this discussion on chemokine structures and functions. The amino-acid alignment of all the human CXC chemokines shown in Fig. 2 is therefore arranged with respect to CXCLS, and references to specific sections of CXCLs will be numbered according to the CXCLS primary sequence. 

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