TMEM266 is a functional voltage sensor regulated by extracellular Zn2+
Voltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/42372 |
| _version_ | 1818026856281014272 |
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| author | Ferenc Papp Suvendu Lomash Orsolya Szilagyi Erika Babikow Jaime Smith Tsg-Hui Chang Maria Isabel Bahamonde Gilman Ewan Stephen Toombes Kenton Jon Swartz |
| author_facet | Ferenc Papp Suvendu Lomash Orsolya Szilagyi Erika Babikow Jaime Smith Tsg-Hui Chang Maria Isabel Bahamonde Gilman Ewan Stephen Toombes Kenton Jon Swartz |
| author_sort | Ferenc Papp |
| collection | DOAJ |
| description | Voltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both of which lack associated pore domains. hTMEM266 is a protein of unknown function that is predicted to contain an S1-S4 domain, along with partially structured cytoplasmic termini. Here we show that hTMEM266 forms oligomers, undergoes both rapid (µs) and slow (ms) structural rearrangements in response to changes in voltage, and contains a Zn2+ binding site that can regulate the slow conformational transition. Our results demonstrate that the S1-S4 domain in hTMEM266 is a functional voltage sensor, motivating future studies to identify cellular processes that may be regulated by the protein. The ability of hTMEM266 to respond to voltage on the µs timescale may be advantageous for designing new genetically encoded voltage indicators. |
| first_indexed | 2024-12-10T04:38:39Z |
| format | Article |
| id | doaj.art-719e833809284aff8bc7609104fd67f5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:38:39Z |
| publishDate | 2019-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-719e833809284aff8bc7609104fd67f52022-12-22T02:01:56ZengeLife Sciences Publications LtdeLife2050-084X2019-02-01810.7554/eLife.42372TMEM266 is a functional voltage sensor regulated by extracellular Zn2+Ferenc Papp0Suvendu Lomash1Orsolya Szilagyi2Erika Babikow3Jaime Smith4Tsg-Hui Chang5Maria Isabel Bahamonde6Gilman Ewan Stephen Toombes7https://orcid.org/0000-0001-8346-1790Kenton Jon Swartz8https://orcid.org/0000-0003-3419-0765Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States; MTA-DE-NAP B Ion Channel Structure-Function Research Group, Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, HungaryMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesMolecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesVoltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both of which lack associated pore domains. hTMEM266 is a protein of unknown function that is predicted to contain an S1-S4 domain, along with partially structured cytoplasmic termini. Here we show that hTMEM266 forms oligomers, undergoes both rapid (µs) and slow (ms) structural rearrangements in response to changes in voltage, and contains a Zn2+ binding site that can regulate the slow conformational transition. Our results demonstrate that the S1-S4 domain in hTMEM266 is a functional voltage sensor, motivating future studies to identify cellular processes that may be regulated by the protein. The ability of hTMEM266 to respond to voltage on the µs timescale may be advantageous for designing new genetically encoded voltage indicators.https://elifesciences.org/articles/42372S1-S4 domainvoltage-sensing domaindivalent cationsfluorescencefluorimetry |
| spellingShingle | Ferenc Papp Suvendu Lomash Orsolya Szilagyi Erika Babikow Jaime Smith Tsg-Hui Chang Maria Isabel Bahamonde Gilman Ewan Stephen Toombes Kenton Jon Swartz TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ eLife S1-S4 domain voltage-sensing domain divalent cations fluorescence fluorimetry |
| title | TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ |
| title_full | TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ |
| title_fullStr | TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ |
| title_full_unstemmed | TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ |
| title_short | TMEM266 is a functional voltage sensor regulated by extracellular Zn2+ |
| title_sort | tmem266 is a functional voltage sensor regulated by extracellular zn2 |
| topic | S1-S4 domain voltage-sensing domain divalent cations fluorescence fluorimetry |
| url | https://elifesciences.org/articles/42372 |
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