Evidence map›Paper›PMID 32459176›Full record

ArticleeLife2020

The architecture of EMC reveals a path for membrane protein insertion.

John P O'Donnell, Ben P Phillips, Yuichi Yagita, Szymon Juszkiewicz, Armin Wagner, Duccio Malinverni, Robert J Keenan, Elizabeth A Miller, Ramanujan S Hegde

Open access · goldAbstract read
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 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
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  5. Review
  6. Review
  7. Review
  8. SARS-CoV-2 membrane protein biogenesis.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Time-resolved photocatalytic proximity labeling uncovers ER proteome dynamics underlying UPR-to-apoptosis transition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Article
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  19. Article
  20. Article

13 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

9 authors at 3 institutions in 2 countries.

John P O'Donnell *MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0002-0571-3603
Ben P Phillips *MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0001-9117-4695
Yuichi Yagita *MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Szymon JuszkiewiczMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0002-3361-7264
Armin WagnerDiamond Light Source, Didcot, United Kingdom.ORCID 0000-0001-8995-7324
Duccio MalinverniMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Robert J KeenanDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.ORCID 0000-0003-1466-0889
Elizabeth A MillerMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0002-1033-8369
Ramanujan S HegdeMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0001-8338-852X
MRC Laboratory of Molecular Biology · GBDiamond Light Source · GBUniversity of Chicago · US

Funding

ER export and the quality control checkpoint during membrane protein biogenesisR01GM078186 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI BULINSKI, JEANNETTE CHLOE, MILLER, ELIZABETH A. · 2006 to 2015
$2.7M
Biogenesis of multi-pass membrane proteins at the ERR01GM130051 · NIGMS · UNIVERSITY OF CHICAGO · PI KEENAN, ROBERT J · 2018 to 2021
$1.3M
Medical Research Council MC_UP_1201/10Medical Research Council MC_UP_A022_1007NIGMS NIH HHS R01 GM078186NIGMS NIH HHS R01 GM130051NIH HHS R01 GM078186NIH HHS R01 GM130051Swiss National Science Foundation P2ELP3_18910Wellcome Trust
6 · The paper itself

Abstract

Approximately 25% of eukaryotic genes code for integral membrane proteins that are assembled at the endoplasmic reticulum. An abundant and widely conserved multi-protein complex termed EMC has been implicated in membrane protein biogenesis, but its mechanism of action is poorly understood. Here, we define the composition and architecture of human EMC using biochemical assays, crystallography of individual subunits, site-specific photocrosslinking, and cryo-EM reconstruction. Our results suggest that EMC's cytosolic domain contains a large, moderately hydrophobic vestibule that can bind a substrate's transmembrane domain (TMD). The cytosolic vestibule leads into a lumenally-sealed, lipid-exposed intramembrane groove large enough to accommodate a single substrate TMD. A gap between the cytosolic vestibule and intramembrane groove provides a potential path for substrate egress from EMC. These findings suggest how EMC facilitates energy-independent membrane insertion of TMDs, explain why only short lumenal domains are translocated by EMC, and constrain models of EMC's proposed chaperone function.

Indexed as

Endoplasmic ReticulumMembrane ProteinsCytosolHEK293 CellsHumansHydrophobic and Hydrophilic InteractionsProtein DomainsSEC Translocation ChannelsEMC2 protein, humanMembrane ProteinsSEC Translocation Channelsbiochemistrychaperonechemical biologyendoplasmic reticulummembrane proteinsmolecular biophysicsnoneorganelle biogenesisstructural biology

Identifiers

PMID32459176
PMCPMC7292650
OpenAlexW3029821273

What OpenQuestion holds

Textmetadata
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.