The A-superfamily of Conotoxins STRUCTURAL AND FUNCTIONAL DIVERGENCE

摘要: The generation of functional novelty in proteins encoded by a gene superfamily is seldom well documented. In this report, we define the A-conotoxin superfamily, which widely expressed venoms predatory cone snails (Conus), and show how products that diverge considerably structure function have arisen within same superfamily. A cDNA clone encoding α-conotoxin GI, first conotoxin characterized, provided initial data identified A-superfamily. Conotoxin precursors A-superfamily were from six Conus species: most (11/16) α-conotoxins, but some (5/16) belong to family excitatory peptides, κA-conotoxins target voltage-gated ion channels. α-Conotoxins are two-disulfide-bridged nicotinic antagonists, 13–19 amino acids length; larger (31–36 acids) with three disulfide bridges. Purification biochemical characterization one peptide, κA-conotoxin MIVA reported; five other predicted conotoxins previously venom-purified. comparative analysis purified venom, their reveal novel post-translational processing, as mutational events leading polymorphism. Patterns sequence divergence Cys codon usage major branches suggest these separate arose.