Structural highlights
Function
[VCP_VACCW] Serves to protect the virus against complement attack by inhibiting both classical and alternative pathways of complement activation. Binds C3b and C4b.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Vaccinia virus complement control protein (VCP), a homolog of the regulators of the complement activation family of proteins, inhibits complement activation through mechanisms similar to human fluid-phase complement regulators factor H and C4b-binding protein. VCP has a heparin-binding activity that assists vaccinia in host interactions. Interaction with cell-surface polyanions like heparin is centrally important in the functioning of fluid-phase complement regulators and is the basis of host-target discrimination by the alternative pathway. We report the structure of VCP in complex with a heparin decasaccharide, which reveals changes in VCP that might be pertinent to complement regulation. Properties that VCP shares with fluid-phase complement regulators suggest that such conformational changes may be of relevance in the functioning of other complement regulators. Additionally, comparison of VCP-heparin interactions with potentially similar interactions in factor H might enable understanding of the structural basis of familial hemolytic uremic syndrome, attributed to mutational disruption of heparin and C3b binding by factor H.
Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.,Ganesh VK, Smith SA, Kotwal GJ, Murthy KH Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8924-9. Epub 2004 Jun 3. PMID:15178763[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Isaacs SN, Kotwal GJ, Moss B. Vaccinia virus complement-control protein prevents antibody-dependent complement-enhanced neutralization of infectivity and contributes to virulence. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):628-32. PMID:1731333
- ↑ Girgis NM, Dehaven BC, Fan X, Viner KM, Shamim M, Isaacs SN. Cell surface expression of the vaccinia virus complement control protein is mediated by interaction with the viral A56 protein and protects infected cells from complement attack. J Virol. 2008 May;82(9):4205-14. doi: 10.1128/JVI.02426-07. Epub 2008 Feb 20. PMID:18287241 doi:http://dx.doi.org/10.1128/JVI.02426-07
- ↑ Ganesh VK, Smith SA, Kotwal GJ, Murthy KH. Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8924-9. Epub 2004 Jun 3. PMID:15178763 doi:10.1073/pnas.0400744101
