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
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 s...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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The American Society for Biochemistry and Molecular Biology Inc
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/50328 |
| _version_ | 1848758449207246848 |
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| author | Henriques, S. Deplazes, Evelyne Lawrence, N. Cheneval, O. Chaousis, S. Inserra, M. Thongyoo, P. King, G. Mark, A. Vetter, I. Craik, D. Schroeder, C. |
| author_facet | Henriques, S. Deplazes, Evelyne Lawrence, N. Cheneval, O. Chaousis, S. Inserra, M. Thongyoo, P. King, G. Mark, A. Vetter, I. Craik, D. Schroeder, C. |
| author_sort | Henriques, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T09:44:10Z |
| format | Journal Article |
| id | curtin-20.500.11937-50328 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:44:10Z |
| publishDate | 2016 |
| publisher | The American Society for Biochemistry and Molecular Biology Inc |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-503282017-09-13T16:07:58Z 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 Henriques, S. Deplazes, Evelyne Lawrence, N. Cheneval, O. Chaousis, S. Inserra, M. Thongyoo, P. King, G. Mark, A. Vetter, I. Craik, D. Schroeder, C. 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. 2016 Journal Article http://hdl.handle.net/20.500.11937/50328 10.1074/jbc.M116.729095 The American Society for Biochemistry and Molecular Biology Inc fulltext |
| spellingShingle | Henriques, S. Deplazes, Evelyne Lawrence, N. Cheneval, O. Chaousis, S. Inserra, M. Thongyoo, P. King, G. Mark, A. Vetter, I. Craik, D. Schroeder, C. 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://hdl.handle.net/20.500.11937/50328 |