Mechanical inhibition of isolated Vo from V/A-ATPase for proton conductance
- Kyoto Sangyo University, Japan
- Osaka University, Japan
- Tokyo University of Pharmacy and Life Sciences, Japan
Abstract
V-ATPase is an energy converting enzyme, coupling ATP hydrolysis/synthesis in the hydrophilic V1 domain, with proton flow through the Vo membrane domain, via rotation of the central rotor complex relative to the surrounding stator apparatus. Upon dissociation from the V1 domain, the Vo domain of the eukaryotic V-ATPase can adopt a physiologically relevant auto-inhibited form in which proton conductance through the Vo domain is prevented, however the molecular mechanism of this inhibition is not fully understood. Using cryo-electron microscopy, we determined the structure of both the holo V/A-ATPase and isolated Vo at near-atomic resolution, respectively. These structures clarify how the isolated Vo domain adopts the auto-inhibited form and how the holo complex prevents formation of the inhibited Vo form.
Data availability
The density maps and the built models for Tth VoV1, Tth V1 (focused refined), and Tth Vo were deposited in EMDB (EMDB ID; 30013, 30014, and 30015) and PDB (PDB ID; 6LY8 for V1 and 6LY9 for isolated Vo), respectively. All data is available in the main text or the supplementary materials.
Article and author information
Author details
Funding
Japan Society for the Promotion of Science (17H03648)
- Ken Yokoyama
Japan Agency for Medical Research and Development (JP17am0101001)
- Kaoru Mitsuoka
Ministry of Education, Culture, Sports, Science, and Technology (12024046)
- Kaoru Mitsuoka
Takeda Science Foundation
- Ken Yokoyama
Japan Science and Technology Agency (JPMJCR1865)
- Kaoru Mitsuoka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Kishikawa 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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Mechanical inhibition of isolated Vo from V/A-ATPase for proton conductance
eLife 9:e56862.
https://doi.org/10.7554/eLife.56862
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