Cryo-EM structure of the KvAP channel reveals a non-domain-swapped voltage sensor topology

  1. Xiao Tao
  2. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, The Rockefeller University, United States

Abstract

Conductance in voltage-gated ion channels is regulated by membrane voltage through structural domains known as voltage sensors. A single structural class of voltage sensor domain exists, but two different modes of voltage sensor attachment to the pore occur in nature: domain-swapped and non-domain-swapped. Since the more thoroughly studied Kv1-7, Nav and Cav channels have domain-swapped voltage sensors, much less is known about non-domain-swapped voltage-gated ion channels. In this paper, using cryo-EM, we show that KvAP from Aeropyrum pernix has non-domain-swapped voltage sensors as well as other unusual features. The new structure, together with previous functional data, suggest that KvAP and the Shaker channel, to which KvAP is most often compared, probably undergo rather different voltage-dependent conformational changes when they open.

Data availability

The B-factor sharpened 3D cryo-EM density map and atomic coordinates of KvAP have been deposited in the Worldwide Protein Data Bank (wwPDB) under accession number EMD-20924 and 6UWM.

The following data sets were generated

Article and author information

Author details

  1. Xiao Tao

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9381-7903
  2. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    mackinn@mail.rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

Funding

Howard Hughes Medical Institute

  • Xiao Tao
  • Roderick MacKinnon

National Institutes of Health (GM43949)

  • Xiao Tao
  • Roderick MacKinnon

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 Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Version history

  1. Received: September 24, 2019
  2. Accepted: November 20, 2019
  3. Accepted Manuscript published: November 22, 2019 (version 1)
  4. Version of Record published: November 28, 2019 (version 2)

Copyright

© 2019, Tao & MacKinnon

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. Xiao Tao
  2. Roderick MacKinnon
(2019)
Cryo-EM structure of the KvAP channel reveals a non-domain-swapped voltage sensor topology
eLife 8:e52164.
https://doi.org/10.7554/eLife.52164

Share this article

https://doi.org/10.7554/eLife.52164

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