title: Diversity of conotoxin gene superfamilies in the venomous snail, Conus victoriae.
abstract: Animal venoms represent a vast library of bioactive peptides and proteins with proven potential, not only as research tools but also as drug leads and therapeutics. This is illustrated clearly by marine cone snails (genus Conus), whose venoms consist of mixtures of hundreds of peptides (conotoxins) with a diverse array of molecular targets, including voltage- and ligand-gated ion channels, G-protein coupled receptors and neurotransmitter transporters. Several conotoxins have found applications as research tools, with some being used or developed as therapeutics. The primary objective of this study was the large-scale discovery of conotoxin sequences from the venom gland of an Australian cone snail species, Conus victoriae. Using cDNA library normalization, high-throughput 454 sequencing, de novo transcriptome assembly and annotation with BLASTX and profile hidden Markov models, we discovered over 100 unique conotoxin sequences from 20 gene superfamilies, the highest diversity of conotoxins so far reported in a single study. Many of the sequences identified are new members of known conotoxin superfamilies, some help to redefine these superfamilies and others represent altogether new classes of conotoxins. In addition, we have demonstrated an efficient combination of methods to mine an animal venom gland and generate a library of sequences encoding bioactive peptides.
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
authors: Samuel D
authors: SD
authors: Robinson
authors: Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, VIC, Australia.
authors: Helena
authors: H
authors: Safavi-Hemami
authors: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC, Australia.
authors: Lachlan D
authors: LD
authors: McIntosh
authors: Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, VIC, Australia.
authors: Anthony W
authors: AW
authors: Purcell
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
authors: Raymond S
authors: RS
authors: Norton
authors: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, VIC, Australia.
authors: Anthony T
authors: AT
authors: Papenfuss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000235:genetics*; D052078:Conus Snail / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein
chemical_list: D020916:Conotoxins; D018076:DNA, Complementary