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dc.contributor.authorHenriques, S.
dc.contributor.authorDeplazes, Evelyne
dc.contributor.authorLawrence, N.
dc.contributor.authorCheneval, O.
dc.contributor.authorChaousis, S.
dc.contributor.authorInserra, M.
dc.contributor.authorThongyoo, P.
dc.contributor.authorKing, G.
dc.contributor.authorMark, A.
dc.contributor.authorVetter, I.
dc.contributor.authorCraik, D.
dc.contributor.authorSchroeder, C.
dc.date.accessioned2017-03-15T22:23:46Z
dc.date.available2017-03-15T22:23:46Z
dc.date.created2017-03-08T06:39:37Z
dc.date.issued2016
dc.identifier.citationHenriques, S. and Deplazes, E. and Lawrence, N. and Cheneval, O. and Chaousis, S. and Inserra, M. and Thongyoo, P. et al. 2016. Interaction of tarantula venom peptide ProTx-II with lipid membranes is a prerequisite for its inhibition of human voltage-gated sodium channel NaV 1.7. Journal of Biological Chemistry. 291 (33): pp. 17049-17065.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/50328
dc.identifier.doi10.1074/jbc.M116.729095
dc.description.abstract

ProTx-II is a disulfide-rich peptide toxin from tarantula venom able to inhibit the human voltage-gated sodium channel 1.7 (hNaV 1.7), a channel reported to be involved in nociception, and thus it might have potential as a pain therapeutic. ProTx-II acts by binding to the membrane-embedded voltage sensor domain of hNaV 1.7, but the precise peptide channel-binding site and the importance of membrane binding on the inhibitory activity of ProTx-II remain unknown. In this study, we examined the structure and membrane-binding properties of ProTx-II and several analogues using NMR spectroscopy, surface plasmon resonance, fluorescence spectroscopy, and molecular dynamics simulations. Our results show a direct correlation between ProTx-II membrane binding affinity and its potency as an hNaV 1.7 channel inhibitor. The data support a model whereby a hydrophobic patch on the ProTx-II surface anchors the molecule at the cell surface in a position that optimizes interaction of the peptide with the binding site on the voltage sensor domain. This is the first study to demonstrate that binding of ProTx-II to the lipid membrane is directly linked to its potency as an hNaV 1.7 channel inhibitor.

dc.publisherThe American Society for Biochemistry and Molecular Biology Inc
dc.titleInteraction of tarantula venom peptide ProTx-II with lipid membranes is a prerequisite for its inhibition of human voltage-gated sodium channel NaV 1.7
dc.typeJournal Article
dcterms.source.volume291
dcterms.source.number33
dcterms.source.startPage17049
dcterms.source.endPage17065
dcterms.source.issn0021-9258
dcterms.source.titleJournal of Biological Chemistry
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access


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