title: Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biological Sciences, National University of Singapore, Singapore. doley@tezu.ernet.in
authors: Robin
authors: R
authors: Doley
authors: Stephen P
authors: SP
authors: Mackessy
authors: R Manjunatha
authors: RM
authors: Kini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004546:Elapid Venoms / Q000235:genetics*; D017815:Elapidae / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D008969:Molecular Sequence Data; D005810:Multigene Family; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D004546:Elapid Venoms; D020033:Protein Isoforms; D015842:Serine Proteinase Inhibitors