Evidence map›Paper›PMID 39900909›Full record

ArticleNature communications2025

A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A.

Ibrahim M Sabbarini, Dvir Reif, Kibum Park, Alexander J McQuown, Anjali R Nelliat, Charlotte Trejtnar, Volker Dötsch, Eugene I Shakhnovich, Andrew W Murray, Vladimir Denic

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. RiboScreenBiomedicines · 2026
    Review
  3. Article
  4. Review
  5. Article
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

10 authors.

Ibrahim M SabbariniDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Dvir ReifDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Kibum ParkDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Alexander J McQuownDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Anjali R NelliatGraduate Program in Systems Biology, Harvard Medical School, Boston, MA, USA.
Charlotte TrejtnarInstitute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt/Main, Germany.ORCID http://orcid.org/0009-0000-4050-4017
Volker DötschInstitute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt/Main, Germany.ORCID http://orcid.org/0000-0001-5720-212X
Eugene I ShakhnovichDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4769-2265
Andrew W MurrayDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0868-6604
Vladimir DenicDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA. vlad.denic@gmail.com.ORCID http://orcid.org/0000-0002-1982-7281

Funding

Mechanistic dissection of eukaryotic protein biogenesis and degradation pathwaysR35GM127136 · NIGMS · HARVARD UNIVERSITY · PI Vladimir Denic · 2018 to 2026
$5.0M
Biophysical foundations of evolutionary dynamicsR35GM139571 · NIGMS · HARVARD UNIVERSITY · PI SHAKHNOVICH, EUGENE I · 2021 to 2025
$3.9M
National Science Foundation (NSF) DGE1745303NIGMS NIH HHS R35 GM127136NIGMS NIH HHS R35 GM139571U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35-GM139571
6 · The paper itself

Abstract

Eukaryotic translation elongation factor 1A (eEF1A) is a highly abundant, multi-domain GTPase. Post-translational steps essential for eEF1A biogenesis are carried out by bespoke chaperones but co-translational mechanisms tailored to eEF1A folding remain unexplored. Here, we use AlphaPulldown to identify Ypl225w (also known as Chp1, Chaperone 1 for eEF1A) as a conserved yeast protein predicted to stabilize the N-terminal, GTP-binding (G) domain of eEF1A against its misfolding propensity, as predicted by computational simulations and validated by microscopy analysis of ypl225wΔ cells. Proteomics and biochemical reconstitution reveal that Ypl225w functions as a co-translational chaperone by forming dual interactions with the eEF1A G domain nascent chain and the UBA domain of ribosome-bound nascent polypeptide-associated complex (NAC). Lastly, we show that Ypl225w primes eEF1A nascent chains for binding to GTP as part of a folding mechanism tightly coupled to chaperone recycling. Our work shows that an ATP-independent chaperone can drive vectorial folding of nascent chains by co-opting G protein nucleotide binding.

Indexed as

Guanosine TriphosphateMolecular ChaperonesPeptide Elongation Factor 1RibosomesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsProtein BindingProtein DomainsProtein FoldingGuanosine TriphosphateMolecular ChaperonesPeptide Elongation Factor 1Saccharomyces cerevisiae Proteins

Identifiers

PMID39900909
PMCPMC11790920

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Registered trials

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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.