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 mammalian serum the bimolecular C3/C5 convertase. This functional similarity of CVF and C3 correlates with many structural similarities, which led to the suggestion that CVF is evolutionally related to C3. We report here the molecular cloning and derived primary structure of CVF. CVF mRNA is > 5924 nucleotides in length. It contains a single open reading frame of 4926 nucleotides, coding for a pre-pro-protein of 1642 amino acids. The deduced amino acid sequence reveals approximately 70% protein similarity to mammalian and human C3 and exceeds 91% in the case of cobra C3. The single-chain pre-pro-CVF consists of a 22-amino acid 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 homologies to C3. Pro-CVF contains five potential N-glycosylation sites, of which only three can be expected to be glycosylated in mature CVF. Like C3, pro-CVF contains 27 cysteine residues and a homologous thioester site in the C3d-like region.
Fritzinger
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DC
Department of Biochemistry and Molecular Biology, Georgetown University, Washington, DC 20007.
Bredehorst
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R
Vogel
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CW
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003176:Complement C3 / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004546:Elapid Venoms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017815:Elapidae; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
D003176:Complement C3; D018076:DNA, Complementary; D004546:Elapid Venoms; D011498:Protein Precursors; C016310:cobra venom factor