8HKQ
ion channel
Summary for 8HKQ
| Entry DOI | 10.2210/pdb8hkq/pdb |
| EMDB information | 34858 |
| Descriptor | Potassium channel subfamily T member 1, ~{N}-[(1~{S})-1-[3-(2-methoxypyridin-4-yl)-1,2,4-oxadiazol-5-yl]ethyl]-2-methyl-5-(trifluoromethyl)pyrazole-3-carboxamide, ZINC ION, ... (5 entities in total) |
| Functional Keywords | ion channel, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 561760.94 |
| Authors | |
| Primary citation | Zhang, J.,Liu, S.,Fan, J.,Yan, R.,Huang, B.,Zhou, F.,Yuan, T.,Gong, J.,Huang, Z.,Jiang, D. Structural basis of human Slo2.2 channel gating and modulation. Cell Rep, 42:112858-112858, 2023 Cited by PubMed Abstract: The sodium-activated Slo2.2 channel is abundantly expressed in the brain, playing a critical role in regulating neuronal excitability. The Na-binding site and the underlying mechanisms of Na-dependent activation remain unclear. Here, we present cryoelectron microscopy (cryo-EM) structures of human Slo2.2 in closed, open, and inhibitor-bound form at resolutions of 2.6-3.2 Å, revealing gating mechanisms of Slo2.2 regulation by cations and a potent inhibitor. The cytoplasmic gating ring domain of the closed Slo2.2 harbors multiple K and Zn sites, which stabilize the channel in the closed conformation. The open Slo2.2 structure reveals at least two Na-sensitive sites where Na binding induces expansion and rotation of the gating ring that opens the inner gate. Furthermore, a potent inhibitor wedges into a pocket formed by pore helix and S6 helix and blocks the pore. Together, our results provide a comprehensive structural framework for the investigation of Slo2.2 channel gating, Na sensation, and inhibition. PubMed: 37494189DOI: 10.1016/j.celrep.2023.112858 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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