Journal article
Mechanism of activation at the selectivity filter of the KcsA K+ channel
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Heer, Florian T
Biozentrum, University of Basel, Basel, Switzerland
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Posson, David J
ORCID
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, United States
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Wojtas-Niziurski, Wojciech
Biozentrum, University of Basel, Basel, Switzerland
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Nimigean, Crina M
ORCID
Department of Biochemistry, Weill Cornell Medical College, New York, United States
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Bernèche, Simon
ORCID
Biozentrum, University of Basel, Basel, Switzerland
Published in:
- eLife. - eLife Sciences Publications, Ltd. - 2017, vol. 6
English
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.
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Language
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Open access status
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gold
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/232054
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