Regulatory switch at the cytoplasmic interface controls TRPV channel gating
Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains...
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Format: | Article |
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eLife Sciences Publications Ltd
2019-05-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/47746 |
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author | Lejla Zubcevic William F Borschel Allen L Hsu Mario J Borgnia Seok-Yong Lee |
author_facet | Lejla Zubcevic William F Borschel Allen L Hsu Mario J Borgnia Seok-Yong Lee |
author_sort | Lejla Zubcevic |
collection | DOAJ |
description | Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains (CTD). The cytoplasmic inter-protomer interface is unique and consists of a CTD coiled around a β-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that the cytoplasmic ring is important for thermoTRPV function, the mechanism by which this unique structure is involved in thermoTRPV gating has not been clear. Here, we present cryo-EM and electrophysiological studies which demonstrate that TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface and that this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening. Furthermore, our studies unveil the role of this interface in the distinct biophysical and physiological properties of individual thermoTRPV subtypes. |
first_indexed | 2024-04-11T09:14:26Z |
format | Article |
id | doaj.art-f3154c9ddaaf4712ab4caceb297014f2 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T09:14:26Z |
publishDate | 2019-05-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
spelling | doaj.art-f3154c9ddaaf4712ab4caceb297014f22022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2019-05-01810.7554/eLife.47746Regulatory switch at the cytoplasmic interface controls TRPV channel gatingLejla Zubcevic0https://orcid.org/0000-0002-1884-9235William F Borschel1https://orcid.org/0000-0003-4064-9026Allen L Hsu2https://orcid.org/0000-0003-2065-3802Mario J Borgnia3https://orcid.org/0000-0001-9159-1413Seok-Yong Lee4https://orcid.org/0000-0002-0662-9921Department of Biochemistry, Duke University School of Medicine, Durham, United StatesDepartment of Biochemistry, Duke University School of Medicine, Durham, United StatesGenome Integrity and Structural Biology Laboratory, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United StatesDepartment of Biochemistry, Duke University School of Medicine, Durham, United States; Genome Integrity and Structural Biology Laboratory, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United StatesDepartment of Biochemistry, Duke University School of Medicine, Durham, United StatesTemperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains (CTD). The cytoplasmic inter-protomer interface is unique and consists of a CTD coiled around a β-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that the cytoplasmic ring is important for thermoTRPV function, the mechanism by which this unique structure is involved in thermoTRPV gating has not been clear. Here, we present cryo-EM and electrophysiological studies which demonstrate that TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface and that this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening. Furthermore, our studies unveil the role of this interface in the distinct biophysical and physiological properties of individual thermoTRPV subtypes.https://elifesciences.org/articles/47746TRP channelion channelligand dependent gatingsensitizationcryo-electronmicroscopyelectrophysiology |
spellingShingle | Lejla Zubcevic William F Borschel Allen L Hsu Mario J Borgnia Seok-Yong Lee Regulatory switch at the cytoplasmic interface controls TRPV channel gating eLife TRP channel ion channel ligand dependent gating sensitization cryo-electronmicroscopy electrophysiology |
title | Regulatory switch at the cytoplasmic interface controls TRPV channel gating |
title_full | Regulatory switch at the cytoplasmic interface controls TRPV channel gating |
title_fullStr | Regulatory switch at the cytoplasmic interface controls TRPV channel gating |
title_full_unstemmed | Regulatory switch at the cytoplasmic interface controls TRPV channel gating |
title_short | Regulatory switch at the cytoplasmic interface controls TRPV channel gating |
title_sort | regulatory switch at the cytoplasmic interface controls trpv channel gating |
topic | TRP channel ion channel ligand dependent gating sensitization cryo-electronmicroscopy electrophysiology |
url | https://elifesciences.org/articles/47746 |
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