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TitlePotassium dependent structural changes in the selectivity filter of HERG potassium channels.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 7470, Year 2024
Publish dateAug 29, 2024
AuthorsCarus H Y Lau / Emelie Flood / Mark J Hunter / Billy J Williams-Noonan / Karen M Corbett / Chai-Ann Ng / James C Bouwer / Alastair G Stewart / Eduardo Perozo / Toby W Allen / Jamie I Vandenberg /
PubMed AbstractThe fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go ...The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to the role they play in regulating cardiac electrical activity. Here, we exploit the K sensitivity of HERG inactivation to determine structures of both a conductive and non-conductive selectivity filter structure of HERG. The conductive state has a canonical cylindrical shaped selectivity filter. The non-conductive state is characterized by flipping of the selectivity filter valine backbone carbonyls to point away from the central axis. The side chain of S620 on the pore helix plays a central role in this process, by coordinating distinct sets of interactions in the conductive, non-conductive, and transition states. Our model represents a distinct mechanism by which ion channels fine tune their activity and could explain the uniquely rapid inactivation kinetics of HERG.
External linksNat Commun / PubMed:39209832 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 3.5 Å
Structure data

45597

9chp

EMDB-45597, PDB-9chp:
Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 300 mM K+
Method: EM (single particle) / Resolution: 3.3 Å

45598

9chq

EMDB-45598, PDB-9chq:
Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 3 mM K+
Method: EM (single particle) / Resolution: 3.0 Å

45599

9chr

EMDB-45599, PDB-9chr:
Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 300 mM K+ without symmetry
Method: EM (single particle) / Resolution: 3.5 Å

45600

9chs

EMDB-45600, PDB-9chs:
Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 3 mM K+ without symmetry
Method: EM (single particle) / Resolution: 3.4 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Ion channel

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