Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes
The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly...
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| Format: | Article |
| Language: | English |
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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/45779 |
| _version_ | 1818026909584326656 |
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| author | Lejla Zubcevic Allen L Hsu Mario J Borgnia Seok-Yong Lee |
| author_facet | Lejla Zubcevic Allen L Hsu Mario J Borgnia Seok-Yong Lee |
| author_sort | Lejla Zubcevic |
| collection | DOAJ |
| description | The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here, we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions. |
| first_indexed | 2024-12-10T04:39:30Z |
| format | Article |
| id | doaj.art-449fe1c19c07414485103caa974b52fb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:39:30Z |
| publishDate | 2019-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-449fe1c19c07414485103caa974b52fb2022-12-22T02:01:55ZengeLife Sciences Publications LtdeLife2050-084X2019-05-01810.7554/eLife.45779Symmetry transitions during gating of the TRPV2 ion channel in lipid membranesLejla Zubcevic0https://orcid.org/0000-0002-1884-9235Allen L Hsu1https://orcid.org/0000-0003-2065-3802Mario J Borgnia2https://orcid.org/0000-0001-9159-1413Seok-Yong Lee3https://orcid.org/0000-0002-0662-9921Department of Biochemistry, Duke University School of Medicine, Durham, United StatesGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, United StatesDepartment of Biochemistry, Duke University School of Medicine, Durham, United States; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, United StatesDepartment of Biochemistry, Duke University School of Medicine, Durham, United StatesThe Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mechanisms of thermoTRPV channels. Interestingly, crystallographic studies of ligand-dependent TRPV2 gating have shown that the TRPV2 channel adopts two-fold symmetric arrangements during the gating cycle. However, it was unclear if crystal packing forces played a role in stabilizing the two-fold symmetric arrangement of the channel. Here, we employ cryo-EM to elucidate the structure of full-length rabbit TRPV2 in complex with the agonist resiniferatoxin (RTx) in nanodiscs and amphipol. We show that RTx induces two-fold symmetric conformations of TRPV2 in both environments. However, the two-fold symmetry is more pronounced in the native-like lipid environment of the nanodiscs. Our data offers insights into a gating pathway in TRPV2 involving symmetry transitions.https://elifesciences.org/articles/45779TRP channelOryctolagus cuniculusheat sensing ion channelCa2+ permeable channelcryo-EMligand gated ion channel |
| spellingShingle | Lejla Zubcevic Allen L Hsu Mario J Borgnia Seok-Yong Lee Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes eLife TRP channel Oryctolagus cuniculus heat sensing ion channel Ca2+ permeable channel cryo-EM ligand gated ion channel |
| title | Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes |
| title_full | Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes |
| title_fullStr | Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes |
| title_full_unstemmed | Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes |
| title_short | Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes |
| title_sort | symmetry transitions during gating of the trpv2 ion channel in lipid membranes |
| topic | TRP channel Oryctolagus cuniculus heat sensing ion channel Ca2+ permeable channel cryo-EM ligand gated ion channel |
| url | https://elifesciences.org/articles/45779 |
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