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

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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

1. Tao X
2. MacKinnon R
(2019) Single particle cryo-EM structure of KvAP
Protein Data Bank, 6UWM.

http://www.rcsb.org/structure/6UWM
1. Tao X
2. MacKinnon R
(2019) Single particle cryo-EM structure of KvAP
EMDataBank, EMD-20924.

http://www.ebi.ac.uk/pdbe/entry/emdb/EMD-20924

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0002-9381-7903
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.

"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.

Copyright

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.