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Open Access Research article

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

Robin Doley1, Stephen P Mackessy2 and R Manjunatha Kini1*

Author Affiliations

1 Protein Science Laboratory, Department of Biological Sciences, National University of Singapore, 117543, Singapore

2 School of Biological Sciences, University of Northern Colorado, Greeley, CO, 80639-0017, USA

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BMC Evolutionary Biology 2009, 9:146  doi:10.1186/1471-2148-9-146

Published: 30 June 2009

Abstract

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.