Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus.
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.
Carfí
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Laboratory of Molecular Medicine, Howard Hughes Medical Institute, The Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.
Smith
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Smolak
P J
PJ
McGrew
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Wiley
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D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D015608:Cowpox virus / Q000737:chemistry*; D006224:Cricetinae; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
D018925:Chemokines; D014759:Viral Envelope Proteins; C072495:immunodominant protein p35, vaccinia virus