Helical jackknives control the gates of the double-pore K+ uptake system KtrAB
- Goethe-University, Germany
- Max Planck Institute of Biophysics, Germany
- University of Osnabrück, Germany
Abstract
Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here we present an inactive ADP-bound structure of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy, which, combined with EPR spectroscopy and molecular dynamics simulations, uncovers a novel regulatory mechanism for ligand-induced action at a distance. Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB dimer to organize into two long helices that penetrate deeply into the regulatory RCK domains, thus connecting nucleotide binding sites and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial pathogenicity factors, the discovery of this functionally relevant inactive conformation may advance structure-guided drug development.
Data availability
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Structure of the K+ transporter KtrAB from Vibrio alginolyticus in the ADP-bound statePublicly available at EBI Protein Data Bank (accession no: EMD-3450).
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KtrAB potassium transporter from Bacillus subtilisPublicly available at Protein Data Bank (accession no: 4J7C).
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (HA 6322/3-1)
- Inga Haenelt
Max Planck Society
- Ahmad Reza Mehdipour
- Deryck J Mills
- Gerhard Hummer
- Janet Vonck
Deutsche Forschungsgemeinschaft (HA 6322/2-1)
- Inga Haenelt
Deutsche Forschungsgemeinschaft (SFB 807)
- Nina Morgner
- Gerhard Hummer
- Inga Haenelt
Deutsche Forschungsgemeinschaft (CEF Macromolecular Complexes)
- Ahmad Reza Mehdipour
- Inga Haenelt
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 Institutes of Health, United States
Version history
- Received: December 15, 2016
- Accepted: May 14, 2017
- Accepted Manuscript published: May 15, 2017 (version 1)
- Accepted Manuscript updated: May 16, 2017 (version 2)
- Version of Record published: May 30, 2017 (version 3)
Copyright
© 2017, Diskowski 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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Helical jackknives control the gates of the double-pore K+ uptake system KtrAB
eLife 6:e24303.
https://doi.org/10.7554/eLife.24303
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