Format

Send to

Choose Destination
Elife. 2017 Oct 10;6. pii: e25844. doi: 10.7554/eLife.25844.

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

Author information

1
SIB Swiss Institute of Bioinformatics, University of Basel, Basel, Switzerland.
2
Biozentrum, University of Basel, Basel, Switzerland.
3
Department of Anesthesiology, Weill Cornell Medical College, New York, United States.
4
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, United States.
5
Department of Biochemistry, Weill Cornell Medical College, New York, United States.

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.

KEYWORDS:

allostery; biophysics; conductance; free energy calculations; gating; ion channel; molecular dynamics; none; pH gated; structural biology

PMID:
28994652
PMCID:
PMC5669632
DOI:
10.7554/eLife.25844
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center