Proton currents constrain structural models of voltage sensor activation
- Yale University School of Medicine, United States
- Sidra Medical Research Center, Qatar
- Virginia Commonwealth University School of Medicine, United States
- University of Oxford, United Kingdom
Abstract
The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H+ conductance (GAQ). Mutation of a highly conserved 'gating charge' residue in the S4 helix (R1H) confers a resting-state H+ 'shuttle' conductance (GSH) in VGCs and Ci VSP, and we now report that R1H is sufficient to reconstitute GSH in Hv1 without abrogating GAQ. Second-site mutations in S3 (D185A/H) and S4 (N4R) experimentally separate GSH and GAQ gating, which report thermodynamically distinct initial and final steps, respectively, in the Hv1 activation pathway. The effects of Hv1 mutations on GSH and GAQ are used to constrain the positions of key side chains in resting- and activated-state VS model structures and provides new insights into the structural basis of VS activation and H+ transfer mechanisms in Hv1.
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Author details
Funding
National Institute of General Medical Sciences (R01GM092908)
- Aaron L Randolph
- Ashley L Bennett
- Ian Scott Ramsey
Wellcome
- Younes Mokrab
- Mark SP Sansom
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Randolph 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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Proton currents constrain structural models of voltage sensor activation
eLife 5:e18017.
https://doi.org/10.7554/eLife.18017
