Journal
MOLECULAR IMMUNOLOGY
Volume 47, Issue 2-3, Pages 332-339Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2009.09.013
Keywords
Chemokines; Chemokine receptors; Immune response; Drug design; Inflammation
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The chemokines play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. These comprise over 50 proteins grouped into four classes, in basis to the arrangement of conserved cysteine residues within the sequence. CXCL9, CXCL10 and CXCL11 are the members of the family of ELR - CXC chemokines and bind the same CXCR3 receptor. During the past few years, several studies have demonstrated a pathogenetic role of CXCR3 and its ligands in many human inflammatory diseases. The blockade of CXCR3 interactions with its ligands has been suggested as a possible therapeutic target for the treatment of these diseases. Therefore, we modelled the three-dimensional structure of CXCL9 and CXCR3, and, successively, of the CXCL9/CXCR3 complex in comparison to CXCL10/CXCR3 and CXCL11/CXCR3 complexes. We have then shown the structural determinants of these interactions and their physico-chemical features. Finally, the interaction residues involved in the formation of the complexes have been highlighted and analyzed in order to be used for drug design. (C) 2009 Elsevier Ltd. All rights reserved.
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