Cobra Venom factor (CVF) is a stable functional co-factor of C3 and C5 convertases present in the venom of various rattle snake species. As part of the alternative pathway of immunological response to pathogens, C3 and C5 convertases are upregulated to induce the formation of membrane attack protein. CVF provides a functional and stable co-factor for convertase formation that can survive much longer than native co-factors and drastically increase the concentration of membrane attack protein which kills self cells and causes necrosis common to snake bites.
Structure
binds factor B, and forms structurally stable C3 and C5 convertases. CVF consists of forming 10 domains: MG1-8 domains, CUB domain and C345c domain. The alpha chain forms regions shown here in white, red purple, green, yellow, blue and cyan respectively. The macroglobular domains MG1-8 of CVF form a ring structure that is similar to C3b and C3c structure, and is termed the . CVF contains eight stabilizing ; three located within C345c, one linking C345c and MG 7, two within MG8, one within LNK and one in the MG5/MG6 interface. A exists within the MG5/MG6 interface, and binds Ca+ with six ligands: Asp517, Asp520, Val518, Pro494, Glu581 through a water molecule. The function of this binding site has not yet been thoroughly defined.
Both the CUB and C345c domains have been implicated in factor B binding and are also structurally similar to C3b and C3c, but are slightly rotated towards each other . The CUB domain is formed by segments of the gamma and beta chains γ- (896-945) and β- (1252-1311). The C345c domain is covalently linked via the The catalytic activity of CVFBb comes from a serine protease, and is located within factor Bb.
Residues 730DE and 736EE at the α'NT region of C3b have been indicated as the major binding sites for factor B binding. Similarly, have been indicated as the corresponding binding sites of factor B. These residues may be responsible for the added stability of CVF, as well as the relative positioning of the CUB and C345c domains.[1]
Convertase formation is upregulated by CVF and is enhanced by the added stability of CVF when compared to native convertases. The absence of binding sites for factor H, factor I, complement receptor 1, decay-accelerating factor (DAF), and membrane co-factor protein in CVF may also contribute to its increased half-life. Factor H and CR1 binding sites in C3b depend on the presence of two glutamic acid residues E744 and E747 located in the MG6 domain. CVF, however, has aspartic acid and lysine residues in these corresponding locations: 728D and 731K. Similarly, segments of the TED domain are absent from CVF and contribute to the lack of binding ability by factor H. Additionally a binding site for properdin, a stabilizing protein, has been proposed at 1381-1414 of the beta chain.
