Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans

Vaccinia virus complement control protein (VCP) inhibits both pathways of c omplement activation through binding the third and fourth components. A hom olog of mammalian regulators of complement activation, its ability to bind heparin endows VCP with additional activities of significance to viral infe ctivity. The structure of VCP reveals a highly extended molecule with a put ative heparin recognition site at its C-terminal end. A second duster of po sitive charges provides a possibly overlapping binding site for both hepari n and complement components. Experiments suggested by the structure indicat e that VCP can bind heparin and control complement simultaneously. This, th e structure of any intact regulator of complement activation, along with at tendant functional insights, will stimulate the design of new therapeutic i nhibitors of complement.