Potassium dependent structural changes in the selectivity filter of HERG potassium channels.

Autor: Lau CHY; Mark Cowley Lidwill Research Program, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.; School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia., Flood E; School of Science, RMIT University, Melbourne, VIC, Australia., Hunter MJ; Mark Cowley Lidwill Research Program, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.; School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia., Williams-Noonan BJ; School of Science, RMIT University, Melbourne, VIC, Australia., Corbett KM; School of Science, RMIT University, Melbourne, VIC, Australia., Ng CA; Mark Cowley Lidwill Research Program, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.; School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia., Bouwer JC; Molecular Horizons and School of Chemistry and Molecular Bioscience, and ARC Centre for Cryoelectron Microscopy of Membrane Proteins, University of Wollongong, Wollongong, NSW, Australia., Stewart AG; School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia.; Computational and Structural Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia., Perozo E; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA., Allen TW; School of Science, RMIT University, Melbourne, VIC, Australia. toby.allen@rmit.edu.au., Vandenberg JI; Mark Cowley Lidwill Research Program, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia. j.vandenberg@victorchang.edu.au.; School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia. j.vandenberg@victorchang.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 29; Vol. 15 (1), pp. 7470. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1038/s41467-024-51208-w
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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