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Structures of the Otopetrin Proton Channels Otop1 and Otop3
Otopetrins (Otop1–Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564688/ https://www.ncbi.nlm.nih.gov/pubmed/31160780 http://dx.doi.org/10.1038/s41594-019-0235-9 |
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author | Saotome, Kei Teng, Bochuan Tsui, Che Chun (Alex) Lee, Wen-Hsin Tu, Yu-Hsiang Kaplan, Joshua P. Sansom, Mark S. P. Liman, Emily R. Ward, Andrew B. |
author_facet | Saotome, Kei Teng, Bochuan Tsui, Che Chun (Alex) Lee, Wen-Hsin Tu, Yu-Hsiang Kaplan, Joshua P. Sansom, Mark S. P. Liman, Emily R. Ward, Andrew B. |
author_sort | Saotome, Kei |
collection | PubMed |
description | Otopetrins (Otop1–Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture, with each subunit forming twelve transmembrane helices divided into structurally similar amino (N) and carboxy (C) domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a central tunnel. In molecular dynamics simulations, hydrophilic vestibules formed by the N and C domains and in the intrasubunit interface between N and C domains form conduits for water entry into the membrane core, suggesting three potential proton conduction pathways. By mutagenesis, we test the roles of charged residues in each putative permeation pathway. Our results provide a structural basis for understanding selective proton permeation and gating of this conserved family of proton channels. |
format | Online Article Text |
id | pubmed-6564688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-65646882019-12-04 Structures of the Otopetrin Proton Channels Otop1 and Otop3 Saotome, Kei Teng, Bochuan Tsui, Che Chun (Alex) Lee, Wen-Hsin Tu, Yu-Hsiang Kaplan, Joshua P. Sansom, Mark S. P. Liman, Emily R. Ward, Andrew B. Nat Struct Mol Biol Article Otopetrins (Otop1–Otop3) comprise one of two known eukaryotic proton-selective channel families. Otop1 is required for otoconia formation and a candidate mammalian sour taste receptor. Here we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture, with each subunit forming twelve transmembrane helices divided into structurally similar amino (N) and carboxy (C) domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a central tunnel. In molecular dynamics simulations, hydrophilic vestibules formed by the N and C domains and in the intrasubunit interface between N and C domains form conduits for water entry into the membrane core, suggesting three potential proton conduction pathways. By mutagenesis, we test the roles of charged residues in each putative permeation pathway. Our results provide a structural basis for understanding selective proton permeation and gating of this conserved family of proton channels. 2019-06-03 2019-06 /pmc/articles/PMC6564688/ /pubmed/31160780 http://dx.doi.org/10.1038/s41594-019-0235-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Saotome, Kei Teng, Bochuan Tsui, Che Chun (Alex) Lee, Wen-Hsin Tu, Yu-Hsiang Kaplan, Joshua P. Sansom, Mark S. P. Liman, Emily R. Ward, Andrew B. Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title | Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title_full | Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title_fullStr | Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title_full_unstemmed | Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title_short | Structures of the Otopetrin Proton Channels Otop1 and Otop3 |
title_sort | structures of the otopetrin proton channels otop1 and otop3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564688/ https://www.ncbi.nlm.nih.gov/pubmed/31160780 http://dx.doi.org/10.1038/s41594-019-0235-9 |
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