- Title
- A constricted opening in Kir channels does not impede potassium conduction
- Creator
- Black, Katrina A.; He, Sitong; Laver, Derek; Robinson, Carol V.; Smith, Brian J.; Gulbis, Jacqueline M.; Jin, Ruitao; Miller, David M.; Bolla, Jani R.; Clarke, Oliver B.; Johnson, Paul; Windley, Monique; Burns, Chirstopher J.; Hill, Adam P.
- Relation
- NHMRC.1006624 http://purl.org/au-research/grants/nhmrc/1006624
- Relation
- Nature Communications Vol. 11, Issue 1, no. 3024
- Publisher Link
- http://dx.doi.org/10.1038/s41467-020-16842-0
- Publisher
- Nature
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- biophysics; computational biology and bioinformatics; structural biology; potassium channel
- Identifier
- http://hdl.handle.net/1959.13/1424334
- Identifier
- uon:38058
- Identifier
- ISSN:2041-1723
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
- Reviewed
- Hits: 6584
- Visitors: 6666
- Downloads: 87
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 2 MB | Adobe Acrobat PDF | View Details Download |