PMID- 11470923 OWN - NLM STAT- MEDLINE DCOM- 20010830 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 98 IP - 16 DP - 2001 Jul 31 TI - Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor. PG - 9008-13 AB - 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. FAU - Seet, B T AU - Seet BT AD - Viral Immunology & Pathogenesis Laboratories, John P. Robarts Research Institute, 1400 Western Road, Room 133, London, ON, Canada N6G 2V4. FAU - Singh, R AU - Singh R FAU - Paavola, C AU - Paavola C FAU - Lau, E K AU - Lau EK FAU - Handel, T M AU - Handel TM FAU - McFadden, G AU - McFadden G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20010724 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (CCI protein, Cowpox virus) RN - 0 (Chemokine CCL2) RN - 0 (Viral Proteins) RN - 0 (Virulence Factors) SB - IM MH - Amino Acid Sequence MH - Chemokine CCL2/*antagonists & inhibitors/chemistry MH - Humans MH - Models, Molecular MH - Molecular Sequence Data MH - Poxviridae/*chemistry MH - Protein Conformation MH - Sequence Homology, Amino Acid MH - Surface Plasmon Resonance MH - Viral Proteins/*pharmacology MH - Virulence Factors PMC - PMC55364 EDAT- 2001/07/27 10:00 MHDA- 2001/08/31 10:01 PMCR- 2002/01/31 CRDT- 2001/07/27 10:00 PHST- 2001/07/27 10:00 [pubmed] PHST- 2001/08/31 10:01 [medline] PHST- 2001/07/27 10:00 [entrez] PHST- 2002/01/31 00:00 [pmc-release] AID - 171069398 [pii] AID - 0693 [pii] AID - 10.1073/pnas.171069398 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9008-13. doi: 10.1073/pnas.171069398. Epub 2001 Jul 24.