Journal article

A constricted opening in Kir channels does not impede potassium conduction

Katrina A Black, Sitong He, Ruitao Jin, David M Miller, Jani R Bolla, Oliver B Clarke, Paul Johnson, Monique Windley, Christopher J Burns, Adam P Hill, Derek Laver, Carol Robinson, Brian J Smith, Jacqueline M Gulbis

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

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 s..

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Grants

Awarded by NHMRC Australia


Awarded by Medical Research Council


Awarded by LIEF Grant


Funding Acknowledgements

We thank Mike Lawrence for advising on low-resolution crystallography. We also thank Peter Colman, Jamie Vandenberg, Matthew Call, Sam el-Ajouz, Pauline Crewther, Agalya Periasamy and Xiaowen Xiao for help and advice. Diffraction data were collected on the MX2 beamline at the Australian Synchrotron, Victoria, Australia. Crystallization trials were carried out at the C3 Parkville Facility by Janet Newman and Shane Seabrook. The project was in part funded by NHMRC Australia Project Grants 1006624 and 1080682, an NHMRC Senior Research Fellowship (J.M.G.), and discretionary funding from The Walter and Eliza Hall Institute. K.A.B. was supported by an Australian Postgraduate Award. R.J. and S.H. acknowledge receipt of Australian Research Training Scholarships. The work in C.V.R group is supported by Medical Research Council Grant MR/N020413/1. Part of this work was undertaken using resources from the National Computational Infrastructure, which is supported by the Australian Government and provided through Intersect Australia Ltd, and through the HPC-GPGPU Facility, which was established with the assistance of LIEF Grant LE170100200. The work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.