MOLECULAR-CLONING AND DERIVED PRIMARY STRUCTURE OF COBRA VENOM FACTOR

Cobra venom factor (CVF) is the complement-activating protein in cobra venom. Like C3b, CVF forms with factor B and factor D in human and ma mmalian serum the bimolecular C3/C5 convertase. This functional simila rity of CVF and C3 correlates with many structural similarities, which led to the suggestion that CVF is evolutionally related to C3. We rep ort here the molecular cloning and derived primary structure of CVF. C VF mRNA is >5924 nucleotides in length. It contains a single open read ing frame of 4926 nucleotides, coding for a pre-pro-protein of 1642 am ino acids. The deduced amino acid sequence reveals approximate to 70% protein similarity to mammalian and human C3 and exceeds 91% in the ca se of cobra C3. The single-chain pre-pro CVF consists of a 22-amino ac id signal sequence, a 627-amino acid alpha-chain, and a 989-amino acid precursor chain for the CVF gamma- and beta-chains. The processing of pro-CVF involves the removal of 4 arginine residues between the alpha - and precursor chains as well as of the C3a-like and C3d-like domains from the precursor chain, thereby confirming the predicted chain homo logies to C3. Pro-CVF contains five potential N-glycosylation sites, o f which only three can be expected to be glycosylated in mature CVF. L ike C3, pro-CVF contains 27 cysteine residues and a homologous thioest er site in the C3d-like region.