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Cell. 2017 Jan 26;168(3):390-399.e11. doi: 10.1016/j.cell.2016.12.030. Epub 2017 Jan 19.

Structural Titration of Slo2.2, a Na+-Dependent K+ Channel.

Author information

1
Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
2
Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA. Electronic address: mackinn@rockefeller.edu.

Abstract

The stable structural conformations that occur along the complete reaction coordinate for ion channel opening have never been observed. In this study, we describe the equilibrium ensemble of structures of Slo2.2, a neuronal Na+-activated K+ channel, as a function of the Na+ concentration. We find that Slo2.2 exists in multiple closed conformations whose relative occupancies are independent of Na+ concentration. An open conformation emerges from an ensemble of closed conformations in a highly Na+-dependent manner, without evidence of Na+-dependent intermediates. In other words, channel opening is a highly concerted, switch-like process. The midpoint of the structural titration matches that of the functional titration. A maximum open conformation probability approaching 1.0 and maximum functional open probability approaching 0.7 imply that, within the class of open channels, there is a subclass that is not permeable to ions.

KEYWORDS:

K(+) channel; Slo2 channel; channel gating mechanism; cryo-electron microscopy; high conductance K(+) channel; ion channel gating; ligand-gated ion channel; molecular structure

PMID:
28111072
PMCID:
PMC5382815
DOI:
10.1016/j.cell.2016.12.030
[Indexed for MEDLINE]
Free PMC Article

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