Open AccessStructure of vaccinia complement protein in complex with heparin and potential implications for complement regulation
Author(s) -
Vannakambadi K. Ganesh,
Scott A. Smith,
Girish J. Kotwal,
Krishna H. M. Murthy
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0400744101
Subject(s) - complement control protein , factor h , complement system , heparin , vaccinia , complement factor i , complement (music) , alternative complement pathway , plasma protein binding , microbiology and biotechnology , complement component 2 , biology , chemistry , immunology , biochemistry , immune system , recombinant dna , gene , phenotype , complementation
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.