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Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus.

ABSTRACT: Most poxviruses, including variola, the causative agent of smallpox, express a secreted protein of 35 kDa, vCCI, which binds CC-chemokines with high affinity. This viral protein competes with the host cellular CC-chemokine receptors (CCRs), reducing inflammation and interfering with the host immune response. Such proteins or derivatives may have therapeutic uses as anti-inflammatory agents. We have determined the crystal structure to 1.85-A resolution of vCCI from cowpox virus, the prototype of this poxvirus virulence factor. The molecule is a beta-sandwich of topology not previously described. A patch of conserved residues on the exposed face of a beta-sheet that is strongly negatively charged might have a role in binding of CC-chemokines, which are positively charged.

SUBMITTER: Carfi A

PROVIDER: S-EPMC22925 | biostudies-literature | 1999 Oct

REPOSITORIES: biostudies-literature

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Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus.

Carfí A A Smith C A CA Smolak P J PJ McGrew J J Wiley D C DC

Proceedings of the National Academy of Sciences of the United States of America 19991001 22

Most poxviruses, including variola, the causative agent of smallpox, express a secreted protein of 35 kDa, vCCI, which binds CC-chemokines with high affinity. This viral protein competes with the host cellular CC-chemokine receptors (CCRs), reducing inflammation and interfering with the host immune response. Such proteins or derivatives may have therapeutic uses as anti-inflammatory agents. We have determined the crystal structure to 1.85-A resolution of vCCI from cowpox virus, the prototype of ...[more]

PMID: 10535930

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