title: The viral CC chemokine-binding protein vCCI inhibits monocyte chemoattractant protein-1 activity by masking its CCR2B-binding site.
abstract: Monocyte chemoattractant protein-1 (MCP-1) is a chemotactic cytokine mainly acting on monocytes and T cells that elicits its biological effects by interacting with the seven-transmembrane helix receptor CCR2B. The vaccinia virus strain Lister and many other poxviruses express soluble proteins (vCCI) that bind MCP-1 and other CC chemokines and inhibit their function. In order to define the interaction site of MCP-1 with vCCI from vaccinia, surface exposed residues of MCP-1 were identified and mutated to alanine. The MCP-1 variants were expressed, purified, and their interaction with vCCI was characterized. The site on MCP-1 for vCCI binding is dominated by arginine 18 with important additional contributions from tyrosine 13 and arginine 24. These residues define a binding site that largely overlaps with the CCR2B receptor interaction site. The viral chemokine-binding protein vCCI thus inhibits the biological function of MCP-1 by directly masking its CCR2B receptor-binding site.
authors.affiliation: Department of Arthritis Biology, Novartis Pharma AG, CH-4002 Basel, Switzerland.
authors.forename: C G
authors.initials: CG
authors.lastname: Beck
authors.forename: C
authors.initials: C
authors.lastname: Studer
authors.forename: J F
authors.initials: JF
authors.lastname: Zuber
authors.forename: B J
authors.initials: BJ
authors.lastname: Demange
authors.forename: U
authors.initials: U
authors.lastname: Manning
authors.forename: R
authors.initials: R
authors.lastname: Urfer
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D003001:Cloning, Molecular; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*; D037521:Virulence Factors
chemical_list: D000911:Antibodies, Monoclonal; C414049:CCI protein, Cowpox virus; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014764:Viral Proteins; D037521:Virulence Factors; D014443:Tyrosine; D001120:Arginine; D000409:Alanine; D002118:Calcium