9CHP

Cryo-EM structure of the human ether-a-go-go related K+ channel (hERG) in 300 mM K+

Summary for 9CHP

• Entry DOI: 10.2210/pdb9chp/pdb
• EMDB information: 45597
• Descriptor: Potassium voltage-gated channel subfamily H member 2 (1 entity in total)
• Functional Keywords: ion channel, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 350733.41

Authors

Lau, C.H.Y.,Hunter, M.J.,Vandenberg, J.I. (deposition date: 2024-07-01, release date: 2024-08-21, Last modification date: 2024-09-11)

Primary citation

Lau, C.H.Y.,Flood, E.,Hunter, M.J.,Williams-Noonan, B.J.,Corbett, K.M.,Ng, C.A.,Bouwer, J.C.,Stewart, A.G.,Perozo, E.,Allen, T.W.,Vandenberg, J.I.
Potassium dependent structural changes in the selectivity filter of HERG potassium channels.
Nat Commun, 15:7470-7470, 2024

PubMed Abstract: 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.

PubMed: 39209832
DOI: 10.1038/s41467-024-51208-w

Experimental method

ELECTRON MICROSCOPY (3.3 Å)