Evidence map›Paper›PMID 33236988›Full record

ArticleeLife2020

Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients.

Lakshmi E Miller-Vedam, Bastian Bräuning, Katerina D Popova, Nicole T Schirle Oakdale, Jessica L Bonnar, Jesuraj R Prabu, Elizabeth A Boydston, Natalia Sevillano, Matthew J Shurtleff, Robert M Stroud and 4 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 89 citations in OpenAlex.

  1. Article
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  12. Review
  13. EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  14. Review
  15. Article
  16. A unifying model for membrane protein biogenesis.Nature structural & molecular biology · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Lakshmi E Miller-Vedam *Molecular, Cellular, and Computational Biophysics Graduate Program, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-2980-7479
Bastian Bräuning *Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0002-7194-2500
Katerina D Popova *Department of Biology, Whitehead Institute, MIT, Cambridge, United States.ORCID 0000-0002-3927-1284
Nicole T Schirle OakdaleDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
Jessica L BonnarDepartment of Biology, Whitehead Institute, MIT, Cambridge, United States.ORCID 0000-0001-5531-4849
Jesuraj R PrabuDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.
Elizabeth A BoydstonDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.ORCID 0000-0001-8365-0436
Natalia SevillanoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Matthew J ShurtleffDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.ORCID 0000-0001-9846-3051
Robert M StroudDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Charles S CraikDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0001-7704-9185
Brenda A SchulmanDepartment of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0002-3083-1126
Adam FrostDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-2231-2577
Jonathan S WeissmanDepartment of Biology, Whitehead Institute, MIT, Cambridge, United States.ORCID 0000-0003-2445-670X
University of California, San Francisco · USMax Planck Institute of Biochemistry · DEHoward Hughes Medical Institute · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
X-ray Screening and Rapid Structure DeterminationP50AI150476 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 2019 to 2021
$14.4M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
STRUCTURE/FUNCTION OF PROTEINS AT MOLECULAR LEVELR01GM024485 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STROUD, ROBERT M · 1985 to 2024
$7.5M
Renewable antibodies to secreted proteins and single and multi-pass cell surfaceP41CA196276 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2014 to 2018
$5.8M
ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Molecular Basis for Transmembrane Conduction & SignalingR37GM024485 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STROUD, ROBERT M · 2007 to 2016
$4.7M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
High Performance Computer for Computational BiosciencesS10OD021596 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 2016 to 2016
$443k
Howard Hughes Medical Institute 55108523NCI NIH HHS P30 CA082103NCI NIH HHS P41 CA196276NIAID NIH HHS P50 AI150476NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R01 GM024485NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R37 GM024485NIGMS NIH HHS T32 GM008284NIH HHS 1DP2OD017690-01NIH HHS 1P41CA196276-01NIH HHS GM24485NIH HHS P50AI150476NIH HHS S10 OD020054NIH HHS S10 OD021596NIH HHS S10 OD021741
6 · The paper itself

Abstract

Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC's multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes.

Indexed as

Blotting, WesternEndoplasmic ReticulumHumansIntracellular MembranesMembrane ProteinsProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentMembrane ProteinsSaccharomyces cerevisiae Proteinscell biologychaperone holdaseelectron microscopyEMCendoplasmic reticulumhumaninsertasemembrane protein biogenesismolecular biophysicsS. cerevisiaestructural biology

Identifiers

PMID33236988
PMCPMC7785296
OpenAlexW3110296556

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.