Optimised deep-targeted proteotranscriptomic profiling reveals unexplored conus toxin diversity and novel cysteine frameworks

Lavergne, Vincent, Harliwong, Ivon, Jones, Alun, Miller, David, Taft, Ryan and Alewood, Paul F. (2015) Optimised deep-targeted proteotranscriptomic profiling reveals unexplored conus toxin diversity and novel cysteine frameworks. Proceedings of the National Acadamy of Sciences of the United States of America, 112 29: E3782-E3791. doi:10.1073/pnas.1501334112


Author Lavergne, Vincent
Harliwong, Ivon
Jones, Alun
Miller, David
Taft, Ryan
Alewood, Paul F.
Title Optimised deep-targeted proteotranscriptomic profiling reveals unexplored conus toxin diversity and novel cysteine frameworks
Journal name Proceedings of the National Acadamy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2015-07-21
Year available 2015
Sub-type Article (original research)
DOI 10.1073/pnas.1501334112
Volume 112
Issue 29
Start page E3782
End page E3791
Total pages 10
Place of publication Washington, DC United States
Publisher National Academy of Sciences
Collection year 2016
Language eng
Formatted abstract
Cone snails are predatory marine gastropods characterized by a sophisticated venom apparatus responsible for the biosynthesis and delivery of complex mixtures of cysteine-rich toxin peptides. These conotoxins fold into small highly structured frameworks, allowing them to potently and selectively interact with heterologous ion channels and receptors. Approximately 2,000 toxins from an estimated number of >70,000 bioactive peptides have been identified in the genus Conus to date. Here, we describe a high-resolution interrogation of the transcriptomes (available at www.ddbj.nig.ac.jp) and proteomes of the diverse compartments of the Conus episcopatus venom apparatus. Using biochemical and bioinformatic tools, we found the highest number of conopeptides yet discovered in a single Conus specimen, with 3,305 novel precursor toxin sequences classified into 9 known superfamilies (A, I1, I2, M, O1, O2, S, T, Z), and identified 16 new superfamilies showing unique signal peptide signatures. We were also able to depict the largest population of venom peptides containing the pharmacologically active C-C-CC-C-C inhibitor cystine knot and CC-C-C motifs (168 and 44 toxins, respectively), as well as 208 new conotoxins displaying odd numbers of cysteine residues derived from known conotoxin motifs. Importantly, six novel cysteine-rich frameworks were revealed which may have novel pharmacology. Finally, analyses of codon usage bias and RNA-editing processes of the conotoxin transcripts demonstrate a specific conservation of the cysteine skeleton at the nucleic acid level and provide new insights about the origin of sequence hypervariablity in mature toxin regions.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 22 Jul 2015, 09:18:51 EST by Susan Allen on behalf of Institute for Molecular Bioscience