Evidence map›Paper›PMID 37199759›Full record

ArticleThe Journal of cell biology2023

A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.

Tino Pleiner, Masami Hazu, Giovani Pinton Tomaleri, Vy N Nguyen, Kurt Januszyk, Rebecca M Voorhees

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  5. Review
  6. Structural evolution of the MTCH family of mitochondrial insertases.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. EMC rectifies the topology of multipass membrane proteins.Nature structural & molecular biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Tino Pleiner *Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0002-5104-0315
Masami Hazu *Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0002-6527-9597
Giovani Pinton Tomaleri *Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0001-9661-6480
Vy N NguyenDivision of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0002-7563-7386
Kurt JanuszykDivision of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0002-9076-4180
Rebecca M VoorheesDivision of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA, USA.ORCID 0000-0003-1640-2293
California Institute of Technology · US

Funding

Protein complex assembly in the ER membraneDP2GM137412 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI VOORHEES, REBECCA · 2019 to 2019
$2.5M
NIGMS NIH HHS DP2 GM137412NIGMS NIH HHS DP2GM137412
6 · The paper itself

Abstract

Tail-anchored (TA) proteins play essential roles in mammalian cells, and their accurate localization is critical for proteostasis. Biophysical similarities lead to mistargeting of mitochondrial TA proteins to the ER, where they are delivered to the insertase, the ER membrane protein complex (EMC). Leveraging an improved structural model of the human EMC, we used mutagenesis and site-specific crosslinking to map the path of a TA protein from its cytosolic capture by methionine-rich loops to its membrane insertion through a hydrophilic vestibule. Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TA proteins. Similarly, this selectivity filter retains the positively charged soluble domains of multipass substrates in the cytosol, thereby ensuring they adopt the correct topology and enforcing the "positive-inside" rule. Substrate discrimination by the EMC provides a biochemical explanation for one role of charge in TA protein sorting and protects compartment integrity by limiting protein misinsertion.

Indexed as

Endoplasmic ReticulumMembrane ProteinsMitochondrial ProteinsHumansProtein ConformationProtein TransportMembrane ProteinsMitochondrial Proteins

Identifiers

PMID37199759
PMCPMC10200711
OpenAlexW4377010659

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.