6NT4
Cryo-EM structure of a human-cockroach hybrid Nav channel bound to alpha-scorpion toxin AaH2.
Summary for 6NT4
| Entry DOI | 10.2210/pdb6nt4/pdb |
| Related | 6NT3 |
| EMDB information | 0500 0501 |
| Descriptor | Sodium channel protein PaFPC1,Sodium channel protein type 9 subunit alpha,Sodium channel protein PaFPC1, Alpha-mammal toxin AaH2, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total) |
| Functional Keywords | sodium channel, scorpion toxin, electrical signaling, fast inactivation, membrane protein |
| Biological source | Periplaneta americana (American cockroach) More |
| Total number of polymer chains | 3 |
| Total formula weight | 201449.97 |
| Authors | Clairfeuille, T.,Rohou, A.,Payandeh, J. (deposition date: 2019-01-28, release date: 2019-02-20, Last modification date: 2024-11-13) |
| Primary citation | Clairfeuille, T.,Cloake, A.,Infield, D.T.,Llongueras, J.P.,Arthur, C.P.,Li, Z.R.,Jian, Y.,Martin-Eauclaire, M.F.,Bougis, P.E.,Ciferri, C.,Ahern, C.A.,Bosmans, F.,Hackos, D.H.,Rohou, A.,Payandeh, J. Structural basis of alpha-scorpion toxin action on Na v channels. Science, 363:-, 2019 Cited by PubMed Abstract: Fast inactivation of voltage-gated sodium (Na) channels is essential for electrical signaling, but its mechanism remains poorly understood. Here we determined the structures of a eukaryotic Na channel alone and in complex with a lethal α-scorpion toxin, AaH2, by electron microscopy, both at 3.5-angstrom resolution. AaH2 wedges into voltage-sensing domain IV (VSD4) to impede fast activation by trapping a deactivated state in which gating charge interactions bridge to the acidic intracellular carboxyl-terminal domain. In the absence of AaH2, the S4 helix of VSD4 undergoes a ~13-angstrom translation to unlatch the intracellular fast-inactivation gating machinery. Highlighting the polypharmacology of α-scorpion toxins, AaH2 also targets an unanticipated receptor site on VSD1 and a pore glycan adjacent to VSD4. Overall, this work provides key insights into fast inactivation, electromechanical coupling, and pathogenic mutations in Na channels. PubMed: 30733386DOI: 10.1126/science.aav8573 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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