Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor

Bruce T. Seet, Rajkumari Singh, Chad Paavola, Elaine K. Lau, Tracy M. Handel, Grant McFadden

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9008-9013
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Jul 31 2001
Externally publishedYes


  • CCR2b
  • Chemokine binding protein
  • Monocyte chemoattractant protein-1
  • Mutagenesis
  • Surface plasmon resonance

ASJC Scopus subject areas

  • General


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