Proton currents constrain structural models of voltage sensor activation
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/18017 |
| _version_ | 1811227692903694336 |
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| author | Aaron L Randolph Younes Mokrab Ashley L Bennett Mark SP Sansom Ian Scott Ramsey |
| author_facet | Aaron L Randolph Younes Mokrab Ashley L Bennett Mark SP Sansom Ian Scott Ramsey |
| author_sort | Aaron L Randolph |
| collection | DOAJ |
| description | 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, providing new insights into the structural basis of VS activation and H+ transfer mechanisms in Hv1. |
| first_indexed | 2024-04-12T09:46:11Z |
| format | Article |
| id | doaj.art-10366edcbbec4e47ae3c07806e5c5983 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:46:11Z |
| publishDate | 2016-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-10366edcbbec4e47ae3c07806e5c59832022-12-22T03:37:56ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.18017Proton currents constrain structural models of voltage sensor activationAaron L Randolph0Younes Mokrab1https://orcid.org/0000-0003-1611-6692Ashley L Bennett2Mark SP Sansom3https://orcid.org/0000-0001-6360-7959Ian Scott Ramsey4https://orcid.org/0000-0002-6432-4253Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, United States; Medical College of Virginia Campus, Virginia Commonwealth University School of Medicine, Richmond, United StatesDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, United States; Medical College of Virginia Campus, Virginia Commonwealth University School of Medicine, Richmond, United StatesDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, United States; Medical College of Virginia Campus, Virginia Commonwealth University School of Medicine, Richmond, United StatesThe 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, providing new insights into the structural basis of VS activation and H+ transfer mechanisms in Hv1.https://elifesciences.org/articles/18017proton transportmembrane channelschannel gatingvoltage sensorprotein structure |
| spellingShingle | Aaron L Randolph Younes Mokrab Ashley L Bennett Mark SP Sansom Ian Scott Ramsey Proton currents constrain structural models of voltage sensor activation eLife proton transport membrane channels channel gating voltage sensor protein structure |
| title | Proton currents constrain structural models of voltage sensor activation |
| title_full | Proton currents constrain structural models of voltage sensor activation |
| title_fullStr | Proton currents constrain structural models of voltage sensor activation |
| title_full_unstemmed | Proton currents constrain structural models of voltage sensor activation |
| title_short | Proton currents constrain structural models of voltage sensor activation |
| title_sort | proton currents constrain structural models of voltage sensor activation |
| topic | proton transport membrane channels channel gating voltage sensor protein structure |
| url | https://elifesciences.org/articles/18017 |
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