RETRACTED: Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans (Retracted article. See vol. 175, pg. 1992, 2018)

被引:112
作者
Murthy, KHM
Smith, SA
Ganesh, VK
Judge, KW
Mullin, N
Barlow, PN
Ogata, CM
Kotwal, GJ
机构
[1] Univ Alabama Birmingham, Ctr Biophys Sci & Engn, Birmingham, AL 35294 USA
[2] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA
[3] Univ Edinburgh, Edinburgh Ctr Prot Technol, Edinburgh EH9 3JJ, Midlothian, Scotland
[4] Brookhaven Natl Lab, Howard Hughes Med Inst, Upton, NY 11973 USA
关键词
D O I
10.1016/S0092-8674(01)00214-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vaccinia virus complement control protein (VCP) inhibits both pathways of complement activation through binding the third and fourth components. A homolog of mammalian regulators of complement activation, its ability to bind heparin endows VCP with additional activities of significance to viral infectivity. The structure of VCP reveals a highly extended molecule with a putative heparin recognition site at its C-terminal end. A second duster of positive charges provides a possibly overlapping binding site for both heparin and complement components. Experiments suggested by the structure indicate that VCP can bind heparin and control complement simultaneously. This, the structure of any intact regulator of complement activation, along with attendant functional insights, will stimulate the design of new therapeutic inhibitors of complement.
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收藏
页码:301 / 311
页数:11
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