Evidence map›Paper›PMID 32820719›Full record

ArticleeLife2020

An ER translocon for multi-pass membrane protein biogenesis.

Philip T McGilvray, S Andrei Anghel, Arunkumar Sundaram, Frank Zhong, Michael J Trnka, James R Fuller, Hong Hu, Alma L Burlingame, Robert J Keenan

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 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
6.8field-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

92 citing papers in PubMed, 145 citations in OpenAlex.

  1. Review
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  10. SARS-CoV-2 membrane protein biogenesis.bioRxiv : the preprint server for biology · 2026
    Article
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32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Philip T McGilvray *Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.ORCID 0000-0002-2693-0076
S Andrei Anghel *Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.
Arunkumar SundaramDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.
Frank ZhongDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.
Michael J TrnkaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-8808-5146
James R FullerDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.ORCID 0000-0002-9029-0923
Hong HuCenter for Research Informatics, The University of Chicago, Chicago, United States.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Robert J KeenanDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.ORCID 0000-0003-1466-0889
University of Chicago · USUniversity of California, San Francisco · US

Funding

The Institute for Translational MedicineUL1TR002389 · NCATS · UNIVERSITY OF CHICAGO · PI Joshua J Jacobs, DAVID O MELTZER · 2017 to 2026
$71.6M
Molecular And Cellular Biology Training ProgramT32GM007183 · NIGMS · UNIVERSITY OF CHICAGO · PI GLICK, BENJAMIN S, RICE, PHOEBE A · 1985 to 2021
$23.9M
Biogenesis of multi-pass membrane proteins at the ERR01GM130051 · NIGMS · UNIVERSITY OF CHICAGO · PI KEENAN, ROBERT J · 2018 to 2021
$1.3M
Defining the cellular role of TMCO1, a glaucoma-linked gene of unknown functionR21EY026719 · NEI · UNIVERSITY OF CHICAGO · PI KEENAN, ROBERT J · 2016 to 2017
$423k
NCATS NIH HHS UL1 TR002389NEI NIH HHS R21 EY026719NIGMS NIH HHS R01 GM130051NIGMS NIH HHS T32 GM007183
6 · The paper itself

Abstract

Membrane proteins with multiple transmembrane domains play critical roles in cell physiology, but little is known about the machinery coordinating their biogenesis at the endoplasmic reticulum. Here we describe a ~ 360 kDa ribosome-associated complex comprising the core Sec61 channel and five accessory factors: TMCO1, CCDC47 and the Nicalin-TMEM147-NOMO complex. Cryo-electron microscopy reveals a large assembly at the ribosome exit tunnel organized around a central membrane cavity. Similar to protein-conducting channels that facilitate movement of transmembrane segments, cytosolic and luminal funnels in TMCO1 and TMEM147, respectively, suggest routes into the central membrane cavity. High-throughput mRNA sequencing shows selective translocon engagement with hundreds of different multi-pass membrane proteins. Consistent with a role in multi-pass membrane protein biogenesis, cells lacking different accessory components show reduced levels of one such client, the glutamate transporter EAAT1. These results identify a new human translocon and provide a molecular framework for understanding its role in multi-pass membrane protein biogenesis.

Indexed as

Protein BiosynthesisCell LineCryoelectron MicroscopyEndoplasmic ReticulumHumansMembrane ProteinsProtein DomainsRibosomesSEC Translocation ChannelsMembrane ProteinsSEC Translocation Channelsbiochemistrybiogenesiscell biologychemical biologyco-translationalendoplasmic reticulumfoldinghumanhuman diseaseinsertionmulti-pass membrane proteinribosometranslocon

Identifiers

PMID32820719
PMCPMC7505659
OpenAlexW3080817826

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.