Conformational equilibrium shift underlies altered K+ channel gating as revealed by NMR

Yuta Iwahashi, Yuki Toyama, Shunsuke Imai, Hiroaki Itoh, Masanori Osawa, Masayuki Inoue and Ichio Shimada ()
Additional contact information
Yuta Iwahashi: The University of Tokyo
Yuki Toyama: The University of Tokyo
Shunsuke Imai: The University of Tokyo
Hiroaki Itoh: The University of Tokyo
Masanori Osawa: The University of Tokyo
Masayuki Inoue: The University of Tokyo
Ichio Shimada: The University of Tokyo

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract The potassium ion (K+) channel plays a fundamental role in controlling K+ permeation across the cell membrane and regulating cellular excitabilities. Mutations in the transmembrane pore reportedly affect the gating transitions of K+ channels, and are associated with the onset of neural disorders. However, due to the lack of structural and dynamic insights into the functions of K+ channels, the structural mechanism by which these mutations cause K+ channel dysfunctions remains elusive. Here, we used nuclear magnetic resonance spectroscopy to investigate the structural mechanism underlying the decreased K+-permeation caused by disease-related mutations, using the prokaryotic K+ channel KcsA. We demonstrated that the conformational equilibrium in the transmembrane region is shifted toward the non-conductive state with the closed intracellular K+-gate in the disease-related mutant. We also demonstrated that this equilibrium shift is attributable to the additional steric contacts in the open-conductive structure, which are evoked by the increased side-chain bulkiness of the residues lining the transmembrane helix. Our results suggest that the alteration in the conformational equilibrium of the intracellular K+-gate is one of the fundamental mechanisms underlying the dysfunctions of K+ channels caused by disease-related mutations.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19005-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19005-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19005-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().