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Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids
Gap junctions form intercellular conduits with a large pore size whose closed and open states regulate communication between adjacent cells. The structural basis of the mechanism by which gap junctions close, however, remains uncertain. Here, we show the cryo–electron microscopy structures of Caenor...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015682/ https://www.ncbi.nlm.nih.gov/pubmed/32095518 http://dx.doi.org/10.1126/sciadv.aax3157 |
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author | Burendei, Batuujin Shinozaki, Ruriko Watanabe, Masakatsu Terada, Tohru Tani, Kazutoshi Fujiyoshi, Yoshinori Oshima, Atsunori |
author_facet | Burendei, Batuujin Shinozaki, Ruriko Watanabe, Masakatsu Terada, Tohru Tani, Kazutoshi Fujiyoshi, Yoshinori Oshima, Atsunori |
author_sort | Burendei, Batuujin |
collection | PubMed |
description | Gap junctions form intercellular conduits with a large pore size whose closed and open states regulate communication between adjacent cells. The structural basis of the mechanism by which gap junctions close, however, remains uncertain. Here, we show the cryo–electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction proteins in an undocked hemichannel form. In the nanodisc-reconstituted structure of the wild-type INX-6 hemichannel, flat double-layer densities obstruct the channel pore. Comparison of the hemichannel structures of a wild-type INX-6 in detergent and nanodisc-reconstituted amino-terminal deletion mutant reveals that lipid-mediated amino-terminal rearrangement and pore obstruction occur upon nanodisc reconstitution. Together with molecular dynamics simulations and electrophysiology functional assays, our results provide insight into the closure of the INX-6 hemichannel in a lipid bilayer before docking of two hemichannels. |
format | Online Article Text |
id | pubmed-7015682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70156822020-02-24 Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids Burendei, Batuujin Shinozaki, Ruriko Watanabe, Masakatsu Terada, Tohru Tani, Kazutoshi Fujiyoshi, Yoshinori Oshima, Atsunori Sci Adv Research Articles Gap junctions form intercellular conduits with a large pore size whose closed and open states regulate communication between adjacent cells. The structural basis of the mechanism by which gap junctions close, however, remains uncertain. Here, we show the cryo–electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction proteins in an undocked hemichannel form. In the nanodisc-reconstituted structure of the wild-type INX-6 hemichannel, flat double-layer densities obstruct the channel pore. Comparison of the hemichannel structures of a wild-type INX-6 in detergent and nanodisc-reconstituted amino-terminal deletion mutant reveals that lipid-mediated amino-terminal rearrangement and pore obstruction occur upon nanodisc reconstitution. Together with molecular dynamics simulations and electrophysiology functional assays, our results provide insight into the closure of the INX-6 hemichannel in a lipid bilayer before docking of two hemichannels. American Association for the Advancement of Science 2020-02-12 /pmc/articles/PMC7015682/ /pubmed/32095518 http://dx.doi.org/10.1126/sciadv.aax3157 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Burendei, Batuujin Shinozaki, Ruriko Watanabe, Masakatsu Terada, Tohru Tani, Kazutoshi Fujiyoshi, Yoshinori Oshima, Atsunori Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title | Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title_full | Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title_fullStr | Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title_full_unstemmed | Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title_short | Cryo-EM structures of undocked innexin-6 hemichannels in phospholipids |
title_sort | cryo-em structures of undocked innexin-6 hemichannels in phospholipids |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015682/ https://www.ncbi.nlm.nih.gov/pubmed/32095518 http://dx.doi.org/10.1126/sciadv.aax3157 |
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