Work

Mechanism of activation at the selectivity filter of the KcsA K+ channel

Year: 2017

Type: article

Abstract: Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary.

Source: eLife

DOI: 10.7554/elife.25844

Authors: Florian T Heer, David J Posson, Wojciech Wojtas-Niziurski, Crina M Nimigean, Simon Bernèche

Institutions: SIB Swiss Institute of Bioinformatics, University of Basel, Weill Cornell Medicine

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funders: Irma T. Hirschl Trust, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, NIH Office of the Director, National Institute of General Medical Sciences