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Structure paper

TitleStructural basis of human Slo2.2 channel gating and modulation.
Journal, issue, pagesCell Rep, Vol. 42, Issue 8, Page 112858, Year 2023
Publish dateJul 25, 2023
AuthorsJiangtao Zhang / Shiqi Liu / Junping Fan / Rui Yan / Bo Huang / Feng Zhou / Tian Yuan / Jianke Gong / Zhuo Huang / Daohua Jiang /
PubMed AbstractThe 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- ...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.
External linksCell Rep / PubMed:37494189
MethodsEM (single particle)
Resolution2.64 - 3.18 Å
Structure data

34827

8hir

EMDB-34827, PDB-8hir:
potassium channels
Method: EM (single particle) / Resolution: 3.18 Å

34847

8hk6

EMDB-34847, PDB-8hk6:
potassium channel
Method: EM (single particle) / Resolution: 2.64 Å

34851

8hkf

EMDB-34851, PDB-8hkf:
ion channel
Method: EM (single particle) / Resolution: 2.66 Å

34853

8hkk

EMDB-34853, PDB-8hkk:
ion channel
Method: EM (single particle) / Resolution: 2.84 Å

34855

8hkm

EMDB-34855, PDB-8hkm:
ion channel
Method: EM (single particle) / Resolution: 2.95 Å

34858

8hkq

EMDB-34858, PDB-8hkq:
ion channel
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-ZN:
Unknown entry

ChemComp-LQ9:
~{N}-[(1~{S})-1-[3-(2-methoxypyridin-4-yl)-1,2,4-oxadiazol-5-yl]ethyl]-2-methyl-5-(trifluoromethyl)pyrazole-3-carboxamide

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / potassium channels / potassium channel / ion channel

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