A constricted opening in Kir channels does not impede potassium conduction

Black, KA; He, S; Jin, R; Miller, DM; Bolla, JR; Clarke, OB; JOHNSON, P; Windley, M; Burns, CJ; Hill, AP; Laver, D; Robinson, CV; Smith, BJ; Gulbis, JM

Author(s): Black, KA; He, S; Jin, R; Miller, DM; Bolla, JR; Clarke, OB; JOHNSON, P; Windley, M; Burns, CJ; Hill, AP; Laver, D; Robinson, CV; Smith, BJ; Gulbis, JM;
Details: Publication Year 2020-06-15,Volume 11,Issue #1,Page 3024
Journal Title: Nature Communications
Publication Type: Journal Article
Abstract: The canonical mechanistic model explaining potassium channel gating is of a conformational change that alternately dilates and constricts a collar-like intracellular entrance to the pore. It is based on the premise that K(+) ions maintain a complete hydration shell while passing between the transmembrane cavity and cytosol, which must be accommodated. To put the canonical model to the test, we locked the conformation of a Kir K(+) channel to prevent widening of the narrow collar. Unexpectedly, conduction was unimpaired in the locked channels. In parallel, we employed all-atom molecular dynamics to simulate K(+) ions moving along the conduction pathway between the lower cavity and cytosol. During simulations, the constriction did not significantly widen. Instead, transient loss of some water molecules facilitated K(+) permeation through the collar. The low free energy barrier to partial dehydration in the absence of conformational change indicates Kir channels are not gated by the canonical mechanism.
Publisher: NPG
Research Division(s): Chemical Biology; Structural Biology
PubMed ID: 32541684
Publisher's Version: https://doi.org/10.1038/s41467-020-16842-0
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-020-16842-0
NHMRC Grants: NHMRC/1006624, NHMRC/1080682,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2020-06-22 11:52:52

Last Modified: 2020-06-22 11:54:54