The gating cycle of a K+ channel at atomic resolution

  1. Luis G Cuello  Is a corresponding author
  2. D Marien Cortes
  3. Eduardo Perozo  Is a corresponding author
  1. Texas Tech University Health Sciences Center, United States
  2. The University of Chicago, United States

Abstract

C-type inactivation in potassium channels helps fine-tune long term channel activity through conformational changes at the selectivity filter. Here, through the use of cross-linked constitutively open constructs, we determined the structures of KcsA's mutants that stabilize the selectivity filter in its conductive (E71A, at 2.25 Å) and deep C-type inactivated (Y82A at 2.4 Å) conformations. These structural snapshots represent KcsA's transient open-conductive (O/O) and the stable open deep C-type inactivated states (O/I), respectively. The present structures provide an unprecedented view of the selectivity filter backbone in its collapsed deep C-type inactivated conformation, highlighting the close interactions with structural waters and the local allosteric interactions that couple activation and inactivation gating. Together with the structures associated with the closed-inactivated state (C/I) and in the well-known closed conductive state (C/O), this work recapitulates, at atomic resolution, the key conformational changes of a potassium channel pore domain as it progresses along its gating cycle.

Article and author information

Author details

  1. Luis G Cuello

    Department of Cell Physiology, Texas Tech University Health Sciences Center, Lubbock, United States
    For correspondence
    luis.cuello@ttuhsc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5192-7568
  2. D Marien Cortes

    Department of Cell Physiology, Texas Tech University Health Sciences Center, Lubbock, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eduardo Perozo

    Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States
    For correspondence
    eperozo@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7132-2793

Funding

National Institute of General Medical Sciences (U54 GM087519)

  • Eduardo Perozo

Welch Foundation (BI-1757)

  • Luis G Cuello

National Institute of General Medical Sciences (1RO1GM097159-01A1)

  • Luis G Cuello

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton J Swartz, National Institutes of Health, United States

Publication history

  1. Received: April 23, 2017
  2. Accepted: November 21, 2017
  3. Accepted Manuscript published: November 22, 2017 (version 1)
  4. Version of Record published: December 1, 2017 (version 2)

Copyright

© 2017, Cuello et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Luis G Cuello
  2. D Marien Cortes
  3. Eduardo Perozo
(2017)
The gating cycle of a K+ channel at atomic resolution
eLife 6:e28032.
https://doi.org/10.7554/eLife.28032

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