8HIR

potassium channels

Summary for 8HIR

• Entry DOI: 10.2210/pdb8hir/pdb
• EMDB information: 34827
• Descriptor: Potassium channel subfamily T member 1, SODIUM ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: potassium channels, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 562842.91

Authors

Jiang, D.H.,Zhang, J.T. (deposition date: 2022-11-21, release date: 2023-08-16)

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

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: 37494189
DOI: 10.1016/j.celrep.2023.112858

Experimental method

ELECTRON MICROSCOPY (3.18 Å)