Mass spectral identification of Vc1.1 and differential distribution of conopeptides in the venom duct of conus victoriae. Effect of post-translational modifications and disulfide isomerisation on bioactivity

Simple item page
dc.contributor.authorTownsend, A.
dc.contributor.authorLivett, B.
dc.contributor.authorBingham, J.
dc.contributor.authorTruong, H.
dc.contributor.authorKaras, J.
dc.contributor.authorO'Donnell, P.
dc.contributor.authorWilliamson, N.
dc.contributor.authorPurcell, A.
dc.contributor.authorScanlon, D.
dc.date.issued2009
dc.description.abstractMolluscs of the genus Conus (cone shells) are carnivorous, feeding on marine worms, small fish and other marine molluscs. They capture their prey by injecting venom containing hundreds of neurally active peptide components. These peptides are classed as conotoxins and consist of small disulfide-bonded peptides exhibiting a high degree of post-translational modifications (PTMs). The functional roles of these modifications remain largely unknown. Two of the most frequently observed modifications are γ-carboxylation of glutamate and hydroxylation of proline (Buczek et al. Cell Mol Life Sci 62:3067, 2005). Vc1.1 is an α-conotoxin from Conus victoriae (Sandall et al. Biochemistry 42(22):6904–6911, 2003) and the only form of this peptide which has been detected in the venom is the γ-glutamate and hydroxyproline (Vc1.1.P6O:E14- Gla) version of the molecule (Jakubowski et al. Toxicon 47(6):688–699, 2006). In order to investigate the role of PTMs, we did mass spectral profiling of the venom duct of C. victoriae looking at changes in mass and the number of peptides detected. We synthesised a number of predicted Vc1.1-PTM peptides together with the three possible disulfide isoforms of Vc1.1 and assessed the possible functional role of the PTM conopeptides by measuring the in vitro activity at the cognate neuronal nicotinic acetylcholine receptors (nAChRs). In addition we looked for their presence Vc1.1 venom by mass spectrometry and by this approach we were able to detect unmodified Vc1.1 in C. victoriae venom for the first time.
dc.description.statementofresponsibilityA. Townsend, B.G. Livett, J.-P. Bingham, H.-T. Truong, J.A. Karas, P. O’Donnell, N.A. Williamson, A.W. Purcell and D. Scanlon
dc.identifier.citationInternational Journal of Peptide Research and Therapeutics, 2009; 15(3):195-203
dc.identifier.doi10.1007/s10989-009-9173-4
dc.identifier.issn1573-3149
dc.identifier.issn1573-3904
dc.identifier.urihttp://hdl.handle.net/2440/75202
dc.language.isoen
dc.publisherSpringer Netherlands
dc.rights© Springer Science+Business Media, LLC 2009
dc.source.urihttps://doi.org/10.1007/s10989-009-9173-4
dc.subjectConotoxins
dc.subjectpost-translational modification
dc.subjectPTM
dc.subjectdisulfide isoforms
dc.subjectVc1.1
dc.subjectneuronal nicotinicacetylcholine receptor
dc.titleMass spectral identification of Vc1.1 and differential distribution of conopeptides in the venom duct of conus victoriae. Effect of post-translational modifications and disulfide isomerisation on bioactivity
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medical Sciences publications