Differential evolution and neofunctionalization of snake venom metalloprotease domains

Brust, Andreas, Sunagar, Kartik, Eivind Undheim, Vetter, Irina, Yang, Daryl C., Casewell, Nicholas R., Ruder, Tim, Jackson, Timothy N. W., Koludarov, Ivan, Alewood, Paul F., Hodgson, Wayne C., Lewis, Richard J., King, Glenn F., Antunes, Agostinho, Hendrikx, Iwan and Fry, Bryan G. (2013) Differential evolution and neofunctionalization of snake venom metalloprotease domains. Molecular and Cellular Proteomics, 12 3: 651-663. doi:10.1074/mcp.M112.023135

Author Brust, Andreas
Sunagar, Kartik
Eivind Undheim
Vetter, Irina
Yang, Daryl C.
Casewell, Nicholas R.
Ruder, Tim
Jackson, Timothy N. W.
Koludarov, Ivan
Alewood, Paul F.
Hodgson, Wayne C.
Lewis, Richard J.
King, Glenn F.
Antunes, Agostinho
Hendrikx, Iwan
Fry, Bryan G.
Total Author Count Override 16
Title Differential evolution and neofunctionalization of snake venom metalloprotease domains
Journal name Molecular and Cellular Proteomics   Check publisher's open access policy
ISSN 1535-9476
Publication date 2013-03
Year available 2012
Sub-type Article (original research)
DOI 10.1074/mcp.M112.023135
Open Access Status
Volume 12
Issue 3
Start page 651
End page 663
Total pages 29
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2013
Language eng
Formatted abstract
Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains.. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and haemorrhagic activities. The cysteine-rich and disintegrinlike domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule’s surface are evolving rapidly whilst the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalised for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich post-synaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type natriuretic peptide instead of the SVMP. The results of this study reinforce the value of studying obscure venoms for biodiscovery of novel investigational ligands.
Keyword Differential domain evolution
Snake venom evolution
Psammophis mossambicus
Echis coloratus
Molecular evolution
Protein evolution and neofunctionalisation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 12 December 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biological Sciences Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 18 Jan 2013, 15:09:22 EST by Susan Allen on behalf of Institute for Molecular Bioscience