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Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins

BACKGROUND: Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-fin...

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Autores principales: Doley, Robin, Mackessy, Stephen P, Kini, R Manjunatha
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711939/
https://www.ncbi.nlm.nih.gov/pubmed/19563684
http://dx.doi.org/10.1186/1471-2148-9-146
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author Doley, Robin
Mackessy, Stephen P
Kini, R Manjunatha
author_facet Doley, Robin
Mackessy, Stephen P
Kini, R Manjunatha
author_sort Doley, Robin
collection PubMed
description BACKGROUND: Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins. RESULTS: Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites. CONCLUSION: ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.
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spelling pubmed-27119392009-07-17 Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins Doley, Robin Mackessy, Stephen P Kini, R Manjunatha BMC Evol Biol Research Article BACKGROUND: Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins. RESULTS: Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites. CONCLUSION: ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions. BioMed Central 2009-06-30 /pmc/articles/PMC2711939/ /pubmed/19563684 http://dx.doi.org/10.1186/1471-2148-9-146 Text en Copyright © 2009 Doley et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Doley, Robin
Mackessy, Stephen P
Kini, R Manjunatha
Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title_full Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title_fullStr Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title_full_unstemmed Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title_short Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins
title_sort role of accelerated segment switch in exons to alter targeting (asset) in the molecular evolution of snake venom proteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711939/
https://www.ncbi.nlm.nih.gov/pubmed/19563684
http://dx.doi.org/10.1186/1471-2148-9-146
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