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

Heer, Florian T. and Posson, David J. and Wojtas-Niziurski, Wojciech and Nimigean, Crina M. and Bernèche, Simon. (2017) Mechanism of activation at the selectivity filter of the KcsA K(+) channel. eLife, 6. e25844.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Computational Biophysics (Bernèche)
UniBasel Contributors:Bernèche, Simon and Heer, Florian and Wojtas-Niziurski, Wojciech
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
e-ISSN:2050-084X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:16 May 2018 06:43
Deposited On:16 May 2018 06:43

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