PMID- 11551937 OWN - NLM STAT- MEDLINE DCOM- 20011226 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 276 IP - 46 DP - 2001 Nov 16 TI - The viral CC chemokine-binding protein vCCI inhibits monocyte chemoattractant protein-1 activity by masking its CCR2B-binding site. PG - 43270-6 AB - 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. FAU - Beck, C G AU - Beck CG AD - Department of Arthritis Biology, Novartis Pharma AG, CH-4002 Basel, Switzerland. FAU - Studer, C AU - Studer C FAU - Zuber, J F AU - Zuber JF FAU - Demange, B J AU - Demange BJ FAU - Manning, U AU - Manning U FAU - Urfer, R AU - Urfer R LA - eng PT - Journal Article DEP - 20010910 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antibodies, Monoclonal) RN - 0 (CCI protein, Cowpox virus) RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Viral Proteins) RN - 0 (Virulence Factors) RN - 42HK56048U (Tyrosine) RN - 94ZLA3W45F (Arginine) RN - OF5P57N2ZX (Alanine) RN - SY7Q814VUP (Calcium) SB - IM MH - Alanine/chemistry MH - Animals MH - Antibodies, Monoclonal/metabolism MH - Arginine/chemistry MH - Binding Sites MH - CHO Cells MH - Calcium/metabolism MH - Chemokine CCL2/*antagonists & inhibitors/*chemistry MH - Cloning, Molecular MH - Cricetinae MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Kinetics MH - Models, Molecular MH - Mutation MH - Protein Binding MH - Receptors, CCR2 MH - Receptors, Chemokine/*chemistry MH - Surface Plasmon Resonance MH - Two-Hybrid System Techniques MH - Tyrosine/chemistry MH - Viral Proteins/*chemistry/*metabolism MH - Virulence Factors EDAT- 2001/09/12 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/09/12 10:00 PHST- 2001/09/12 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/09/12 10:00 [entrez] AID - S0021-9258(19)82963-0 [pii] AID - 10.1074/jbc.M106305200 [doi] PST - ppublish SO - J Biol Chem. 2001 Nov 16;276(46):43270-6. doi: 10.1074/jbc.M106305200. Epub 2001 Sep 10.