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;
Publication Year 2020-06-15, Volume 11, Issue #1, Page 3024
- Journal Title
- Nature Communications
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- Chemical Biology; Structural Biology
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-06-22 11:52:52Last Modified: 2020-06-22 11:54:54