title: Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor.
abstract: Poxviruses express a family of secreted proteins that bind with high affinity to chemokines and antagonize the interaction with their cognate G protein-coupled receptors (GPCRs). These viral inhibitors are novel in structure and, unlike cellular chemokine receptors, are able to specifically interact with most, if not all, CC-chemokines. We therefore sought to define the structural features of CC-chemokines that facilitate this broad-spectrum interaction. Here, we identify the residues present on human monocyte chemoattractant protein-1 (MCP-1) that are required for high-affinity interaction with the vaccinia virus 35-kDa CC-chemokine binding protein (VV-35kDa). Not only do these residues correspond to those required for interaction with the cognate receptor CCR2b but they are also conserved among many CC-chemokines. Thus, the results provide a structural basis for the ability of VV-35kDa to promiscuously recognize CC-chemokines and block binding to their receptors.
authors.affiliation: Viral Immunology & Pathogenesis Laboratories, John P. Robarts Research Institute, 1400 Western Road, Room 133, London, ON, Canada N6G 2V4.
authors.forename: B T
authors.initials: BT
authors.lastname: Seet
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Paavola
authors.forename: E K
authors.initials: EK
authors.lastname: Lau
authors.forename: T M
authors.initials: TM
authors.lastname: Handel
authors.forename: G
authors.initials: G
authors.lastname: McFadden
mesh_terms: D000595:Amino Acid Sequence; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011212:Poxviridae / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014764:Viral Proteins / Q000494:pharmacology*; D037521:Virulence Factors
chemical_list: C414049:CCI protein, Cowpox virus; D018932:Chemokine CCL2; D014764:Viral Proteins; D037521:Virulence Factors