Proton currents constrain structural models of voltage sensor activation

Aaron L. Randolph, Younes Mokrab, Ashley L. Bennett, Mark S P Sansom, Ian Scott Ramsey

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 GSHand GAQgating, which report thermodynamically distinct initial and final steps, respectively, in the Hv1 activation pathway. The effects of Hv1 mutations on GSHand GAQare used to constrain the positions of key side chains in resting-and activated-state VS model structures, providing new insights into the structural basis of VS activation and H+transfer mechanisms in Hv1.

Original languageEnglish
Article numbere18017
JournaleLife
Volume5
Issue numberAUGUST
DOIs
Publication statusPublished - 30 Aug 2016

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Structural Models
Protons
Chemical activation
Mutation
Sensors
Electric potential
Model structures
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Randolph, A. L., Mokrab, Y., Bennett, A. L., Sansom, M. S. P., & Ramsey, I. S. (2016). Proton currents constrain structural models of voltage sensor activation. eLife, 5(AUGUST), [e18017]. https://doi.org/10.7554/eLife.18017

Proton currents constrain structural models of voltage sensor activation. / Randolph, Aaron L.; Mokrab, Younes; Bennett, Ashley L.; Sansom, Mark S P; Ramsey, Ian Scott.

In: eLife, Vol. 5, No. AUGUST, e18017, 30.08.2016.

Research output: Contribution to journalArticle

Randolph, AL, Mokrab, Y, Bennett, AL, Sansom, MSP & Ramsey, IS 2016, 'Proton currents constrain structural models of voltage sensor activation', eLife, vol. 5, no. AUGUST, e18017. https://doi.org/10.7554/eLife.18017
Randolph AL, Mokrab Y, Bennett AL, Sansom MSP, Ramsey IS. Proton currents constrain structural models of voltage sensor activation. eLife. 2016 Aug 30;5(AUGUST). e18017. https://doi.org/10.7554/eLife.18017
Randolph, Aaron L. ; Mokrab, Younes ; Bennett, Ashley L. ; Sansom, Mark S P ; Ramsey, Ian Scott. / Proton currents constrain structural models of voltage sensor activation. In: eLife. 2016 ; Vol. 5, No. AUGUST.
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