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Structure of the ER membrane complex, a transmembrane-domain insertase

The ER membrane complex (EMC) cooperates with the Sec61 translocon to co-translationally insert a transmembrane helix (TMH) of many multi-pass integral membrane proteins into the ER membrane, and it is also responsible for inserting the TMH of some tail-anchored proteins (1–3). How EMC accomplishes...

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Autores principales: Bai, Lin, You, Qinglong, Feng, Xiang, Kovach, Amanda, Li, Huilin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442705/
https://www.ncbi.nlm.nih.gov/pubmed/32494008
http://dx.doi.org/10.1038/s41586-020-2389-3
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author Bai, Lin
You, Qinglong
Feng, Xiang
Kovach, Amanda
Li, Huilin
author_facet Bai, Lin
You, Qinglong
Feng, Xiang
Kovach, Amanda
Li, Huilin
author_sort Bai, Lin
collection PubMed
description The ER membrane complex (EMC) cooperates with the Sec61 translocon to co-translationally insert a transmembrane helix (TMH) of many multi-pass integral membrane proteins into the ER membrane, and it is also responsible for inserting the TMH of some tail-anchored proteins (1–3). How EMC accomplishes this feat has been unclear. Here we report the first cryo-EM structure of the eukaryotic EMC. We found that the Saccharomyces cerevisiae EMC contains eight subunits (Emc1–6, 7, and 10); has a large lumenal region and a smaller cytosolic region; and has a transmembrane region formed by Emc4, 5, and 6 plus the transmembrane domains (TMDs) of Emc1 and 3. We identified a 5-TMH fold centered around Emc3 that resembles the prokaryotic insertase YidC and that delineates a largely hydrophilic client pocket. The TMD of Emc4 tilts away from the main transmembrane region of EMC and is partially mobile. Mutational studies demonstrated that Emc4 flexibility and the hydrophilicity of the client pocket are required for EMC function. The EMC structure reveals a remarkable evolutionary conservation with the prokaryotic insertases (4,5); suggests a similar mechanism of TMH insertion; and provides a framework for detailed understanding of membrane insertion for numerous eukaryotic integral membrane proteins and tail-anchored proteins.
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spelling pubmed-74427052020-12-03 Structure of the ER membrane complex, a transmembrane-domain insertase Bai, Lin You, Qinglong Feng, Xiang Kovach, Amanda Li, Huilin Nature Article The ER membrane complex (EMC) cooperates with the Sec61 translocon to co-translationally insert a transmembrane helix (TMH) of many multi-pass integral membrane proteins into the ER membrane, and it is also responsible for inserting the TMH of some tail-anchored proteins (1–3). How EMC accomplishes this feat has been unclear. Here we report the first cryo-EM structure of the eukaryotic EMC. We found that the Saccharomyces cerevisiae EMC contains eight subunits (Emc1–6, 7, and 10); has a large lumenal region and a smaller cytosolic region; and has a transmembrane region formed by Emc4, 5, and 6 plus the transmembrane domains (TMDs) of Emc1 and 3. We identified a 5-TMH fold centered around Emc3 that resembles the prokaryotic insertase YidC and that delineates a largely hydrophilic client pocket. The TMD of Emc4 tilts away from the main transmembrane region of EMC and is partially mobile. Mutational studies demonstrated that Emc4 flexibility and the hydrophilicity of the client pocket are required for EMC function. The EMC structure reveals a remarkable evolutionary conservation with the prokaryotic insertases (4,5); suggests a similar mechanism of TMH insertion; and provides a framework for detailed understanding of membrane insertion for numerous eukaryotic integral membrane proteins and tail-anchored proteins. 2020-06-03 2020-08 /pmc/articles/PMC7442705/ /pubmed/32494008 http://dx.doi.org/10.1038/s41586-020-2389-3 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
Bai, Lin
You, Qinglong
Feng, Xiang
Kovach, Amanda
Li, Huilin
Structure of the ER membrane complex, a transmembrane-domain insertase
title Structure of the ER membrane complex, a transmembrane-domain insertase
title_full Structure of the ER membrane complex, a transmembrane-domain insertase
title_fullStr Structure of the ER membrane complex, a transmembrane-domain insertase
title_full_unstemmed Structure of the ER membrane complex, a transmembrane-domain insertase
title_short Structure of the ER membrane complex, a transmembrane-domain insertase
title_sort structure of the er membrane complex, a transmembrane-domain insertase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442705/
https://www.ncbi.nlm.nih.gov/pubmed/32494008
http://dx.doi.org/10.1038/s41586-020-2389-3
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