The A-superfamily of Conotoxins

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

• Publication year

  2004

• Venue

  Journal of Biological Chemistry

• Publication date

  2004-04-23

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M309654200PMID 14701840
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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