2N9T
NMR solution structure of ProTx-II
Summary for 2N9T
| Entry DOI | 10.2210/pdb2n9t/pdb |
| NMR Information | BMRB: 25917 |
| Descriptor | Beta/omega-theraphotoxin-Tp2a (1 entity in total) |
| Functional Keywords | toxin, cystine knot |
| Biological source | Thrixopelma pruriens (green velvet) |
| Cellular location | Secreted : P83476 |
| Total number of polymer chains | 1 |
| Total formula weight | 3839.69 |
| Authors | Schroeder, C.I. (deposition date: 2015-12-08, release date: 2016-07-06, Last modification date: 2024-11-20) |
| Primary citation | Henriques, S.T.,Deplazes, E.,Lawrence, N.,Cheneval, O.,Chaousis, S.,Inserra, M.,Thongyoo, P.,King, G.F.,Mark, A.E.,Vetter, I.,Craik, D.J.,Schroeder, C.I. Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel NaV1.7. J.Biol.Chem., 291:17049-17065, 2016 Cited by PubMed Abstract: ProTx-II is a disulfide-rich peptide toxin from tarantula venom able to inhibit the human voltage-gated sodium channel 1.7 (hNaV1.7), 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 hNaV1.7, 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 hNaV1.7 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 hNaV1.7 channel inhibitor. PubMed: 27311819DOI: 10.1074/jbc.M116.729095 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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