Cryo-EM structure of the KvAP channel reveals a non-domain-swapped voltage sensor topology
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.
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Single particle cryo-EM structure of KvAPProtein Data Bank, 6UWM.
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Single particle cryo-EM structure of KvAPEMDataBank, EMD-20924.
Article and author information
Author details
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
- Kenton J Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Version history
- Received: September 24, 2019
- Accepted: November 20, 2019
- Accepted Manuscript published: November 22, 2019 (version 1)
- 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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