9GTQ
NavMs F208L Apo
Summary for 9GTQ
| Entry DOI | 10.2210/pdb9gtq/pdb |
| Descriptor | Ion transport protein, PHOSPHATIDYLETHANOLAMINE, HEGA-10, ... (5 entities in total) |
| Functional Keywords | volatge-gated sodium channel, membrane protein |
| Biological source | Magnetococcus marinus MC-1 |
| Total number of polymer chains | 1 |
| Total formula weight | 34281.87 |
| Authors | Hollingworth, D.,Wallace, B.A. (deposition date: 2024-09-18, release date: 2025-10-01, Last modification date: 2026-09-02) |
| Primary citation | Hollingworth, D.,Herold, K.F.,Kelly, G.,Mykhaylyk, V.B.,Wallace, B.A.,Hemmings Jr., H.C. Volatile anaesthetics modulate voltage-gated sodium channel function at a site directly linked to channel gating. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Voltage-gated sodium channels (VGSCs) mediate neuronal excitability and synaptic transmission and are functionally relevant targets for volatile anaesthetic (VA) actions. Here, we show that multiple VAs at clinically relevant concentrations share binding sites on NavMs, a prokaryotic VGSC. Sevoflurane, a representative VA, interacts with NavMs and NaChBac with functional effects paralleling those on human VGSCs, including modulation of channel inactivation. X-ray crystallography of purified NavMs reveals an atomic-resolution VA binding site in a VGSC, in which sevoflurane displaces lipid to occupy a membrane-embedded hydrophobic pocket. Alanine substitution of an invariant tyrosine within this binding pocket abolishes sevoflurane binding and eliminates the sevoflurane-induced hyperpolarising shift of steady-state inactivation. Sevoflurane modulates both fast and slow inactivation of human Nav1.1, demonstrating VA modulation of steady-state slow inactivation in a neuronal VGSC. Supporting evidence shows that VAs interact with homologous sites in human VGSCs. These findings define a VA binding site in VGSCs that supports a membrane-assisted pathway for modulating channel gating and neuronal activity in general anaesthesia. PubMed: 42321197DOI: 10.1038/s41467-026-74518-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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