Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/75130
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Type: Journal article
Title: Novel venom proteins produced by differential domain-expression strategies in beaded lizards and gila monsters (genus Heloderma)
Author: Fry, B.
Roelants, K.
Winter, K.
Hodgson, W.
Griesman, L.
Kwok, H.
Scanlon, D.
Karas, J.
Shaw, C.
Wong, L.
Norman, J.
Citation: Molecular Biology and Evolution, 2010; 27(2):395-407
Publisher: Oxford Univ Press
Issue Date: 2010
ISSN: 0737-4038
1537-1719
Statement of
Responsibility: 
Bryan G. Fry, Kim Roelants, Kelly Winter, Wayne C. Hodgson, Laura Griesman, Hang Fai Kwok, Denis Scanlon, John Karas, Chris Shaw, Lily Wong and Janette A. Norman
Abstract: The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/ glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.
Keywords: Venom; adaptive evolution; molecular evolution; protein; toxin; Heloderma; byetta; exendin
Rights: © The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.
RMID: 0020106193
DOI: 10.1093/molbev/msp251
Appears in Collections:Medical Sciences publications

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