Cryo-EM structure of the mechanically activated ion channel OSCA1.2
Mechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not ex...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/41845 |
| _version_ | 1811180462780973056 |
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| author | Sebastian Jojoa-Cruz Kei Saotome Swetha E Murthy Che Chun Alex Tsui Mark SP Sansom Ardem Patapoutian Andrew B Ward |
| author_facet | Sebastian Jojoa-Cruz Kei Saotome Swetha E Murthy Che Chun Alex Tsui Mark SP Sansom Ardem Patapoutian Andrew B Ward |
| author_sort | Sebastian Jojoa-Cruz |
| collection | DOAJ |
| description | Mechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not explored. Here, we elucidate high resolution cryo-electron microscopy structures of OSCA1.2, revealing a dimeric architecture containing eleven transmembrane helices per subunit and surprising topological similarities to TMEM16 proteins. We locate the ion permeation pathway within each subunit by demonstrating that a conserved acidic residue is a determinant of channel conductance. Molecular dynamics simulations reveal membrane interactions, suggesting the role of lipids in OSCA1.2 gating. These results lay a foundation to decipher how the structural organization of OSCA/TMEM63 is suited for their roles as MA ion channels. |
| first_indexed | 2024-04-11T09:02:29Z |
| format | Article |
| id | doaj.art-23cb84194ec248b0adcd920616c63087 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:02:29Z |
| publishDate | 2018-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-23cb84194ec248b0adcd920616c630872022-12-22T04:32:43ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.41845Cryo-EM structure of the mechanically activated ion channel OSCA1.2Sebastian Jojoa-Cruz0https://orcid.org/0000-0002-4392-3898Kei Saotome1https://orcid.org/0000-0002-4135-5356Swetha E Murthy2https://orcid.org/0000-0001-9580-3380Che Chun Alex Tsui3https://orcid.org/0000-0003-4886-9824Mark SP Sansom4https://orcid.org/0000-0001-6360-7959Ardem Patapoutian5https://orcid.org/0000-0003-0726-7034Andrew B Ward6https://orcid.org/0000-0001-7153-3769Department of Integrative Structural and Computational Biology, The Scripps Research Institute, California, United StatesDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, California, United States; Department of Neuroscience, Dorris Neuroscience Center, Howard Hughes Medical Institute, The Scripps Research Institute, California, United StatesDepartment of Neuroscience, Dorris Neuroscience Center, Howard Hughes Medical Institute, The Scripps Research Institute, California, United StatesDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, California, United States; Department of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Neuroscience, Dorris Neuroscience Center, Howard Hughes Medical Institute, The Scripps Research Institute, California, United StatesDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, California, United StatesMechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not explored. Here, we elucidate high resolution cryo-electron microscopy structures of OSCA1.2, revealing a dimeric architecture containing eleven transmembrane helices per subunit and surprising topological similarities to TMEM16 proteins. We locate the ion permeation pathway within each subunit by demonstrating that a conserved acidic residue is a determinant of channel conductance. Molecular dynamics simulations reveal membrane interactions, suggesting the role of lipids in OSCA1.2 gating. These results lay a foundation to decipher how the structural organization of OSCA/TMEM63 is suited for their roles as MA ion channels.https://elifesciences.org/articles/41845ion channelelectron microscopymechanotransduction |
| spellingShingle | Sebastian Jojoa-Cruz Kei Saotome Swetha E Murthy Che Chun Alex Tsui Mark SP Sansom Ardem Patapoutian Andrew B Ward Cryo-EM structure of the mechanically activated ion channel OSCA1.2 eLife ion channel electron microscopy mechanotransduction |
| title | Cryo-EM structure of the mechanically activated ion channel OSCA1.2 |
| title_full | Cryo-EM structure of the mechanically activated ion channel OSCA1.2 |
| title_fullStr | Cryo-EM structure of the mechanically activated ion channel OSCA1.2 |
| title_full_unstemmed | Cryo-EM structure of the mechanically activated ion channel OSCA1.2 |
| title_short | Cryo-EM structure of the mechanically activated ion channel OSCA1.2 |
| title_sort | cryo em structure of the mechanically activated ion channel osca1 2 |
| topic | ion channel electron microscopy mechanotransduction |
| url | https://elifesciences.org/articles/41845 |
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