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https://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. |
DOI: | 10.1093/molbev/msp251 |
Grant ID: | ARC |
Published version: | http://dx.doi.org/10.1093/molbev/msp251 |
Appears in Collections: | Aurora harvest Medical Sciences publications |
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