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Structure of the native Sec61 protein-conducting channel
In mammalian cells, secretory and membrane proteins are translocated across or inserted into the endoplasmic reticulum (ER) membrane by the universally conserved protein-conducting channel Sec61, which has been structurally studied in isolated, detergent-solubilized states. Here we structurally and...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598622/ https://www.ncbi.nlm.nih.gov/pubmed/26411746 http://dx.doi.org/10.1038/ncomms9403 |
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author | Pfeffer, Stefan Burbaum, Laura Unverdorben, Pia Pech, Markus Chen, Yuxiang Zimmermann, Richard Beckmann, Roland Förster, Friedrich |
author_facet | Pfeffer, Stefan Burbaum, Laura Unverdorben, Pia Pech, Markus Chen, Yuxiang Zimmermann, Richard Beckmann, Roland Förster, Friedrich |
author_sort | Pfeffer, Stefan |
collection | PubMed |
description | In mammalian cells, secretory and membrane proteins are translocated across or inserted into the endoplasmic reticulum (ER) membrane by the universally conserved protein-conducting channel Sec61, which has been structurally studied in isolated, detergent-solubilized states. Here we structurally and functionally characterize native, non-solubilized ribosome-Sec61 complexes on rough ER vesicles using cryo-electron tomography and ribosome profiling. Surprisingly, the 9-Å resolution subtomogram average reveals Sec61 in a laterally open conformation, even though the channel is not in the process of inserting membrane proteins into the lipid bilayer. In contrast to recent mechanistic models for polypeptide translocation and insertion, our results indicate that the laterally open conformation of Sec61 is the only conformation present in the ribosome-bound translocon complex, independent of its functional state. Consistent with earlier functional studies, our structure suggests that the ribosome alone, even without a nascent chain, is sufficient for lateral opening of Sec61 in a lipid environment. |
format | Online Article Text |
id | pubmed-4598622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45986222015-10-21 Structure of the native Sec61 protein-conducting channel Pfeffer, Stefan Burbaum, Laura Unverdorben, Pia Pech, Markus Chen, Yuxiang Zimmermann, Richard Beckmann, Roland Förster, Friedrich Nat Commun Article In mammalian cells, secretory and membrane proteins are translocated across or inserted into the endoplasmic reticulum (ER) membrane by the universally conserved protein-conducting channel Sec61, which has been structurally studied in isolated, detergent-solubilized states. Here we structurally and functionally characterize native, non-solubilized ribosome-Sec61 complexes on rough ER vesicles using cryo-electron tomography and ribosome profiling. Surprisingly, the 9-Å resolution subtomogram average reveals Sec61 in a laterally open conformation, even though the channel is not in the process of inserting membrane proteins into the lipid bilayer. In contrast to recent mechanistic models for polypeptide translocation and insertion, our results indicate that the laterally open conformation of Sec61 is the only conformation present in the ribosome-bound translocon complex, independent of its functional state. Consistent with earlier functional studies, our structure suggests that the ribosome alone, even without a nascent chain, is sufficient for lateral opening of Sec61 in a lipid environment. Nature Pub. Group 2015-09-28 /pmc/articles/PMC4598622/ /pubmed/26411746 http://dx.doi.org/10.1038/ncomms9403 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Pfeffer, Stefan Burbaum, Laura Unverdorben, Pia Pech, Markus Chen, Yuxiang Zimmermann, Richard Beckmann, Roland Förster, Friedrich Structure of the native Sec61 protein-conducting channel |
title | Structure of the native Sec61 protein-conducting channel |
title_full | Structure of the native Sec61 protein-conducting channel |
title_fullStr | Structure of the native Sec61 protein-conducting channel |
title_full_unstemmed | Structure of the native Sec61 protein-conducting channel |
title_short | Structure of the native Sec61 protein-conducting channel |
title_sort | structure of the native sec61 protein-conducting channel |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598622/ https://www.ncbi.nlm.nih.gov/pubmed/26411746 http://dx.doi.org/10.1038/ncomms9403 |
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