Evidence map›Paper›PMID 36493755›Full record

ArticleCell2022

Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT.

Daniel Gestaut, Yanyan Zhao, Junsun Park, Boxue Ma, Alexander Leitner, Miranda Collier, Grigore Pintilie, Soung-Hun Roh, Wah Chiu, Judith Frydman

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.7field-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

52 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Chemical reviews · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. CryoEM Strategies for Elucidating the Closed State Architecture of CCT.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  16. The Open Conformation of CCT: How to Achieve High Resolution Using CryoEM.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 4 countries.

Daniel GestautDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Yanyan ZhaoDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Junsun ParkSchool of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
Boxue MaDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Alexander LeitnerInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland.
Miranda CollierDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Grigore PintilieDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Soung-Hun RohSchool of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea. Electronic address: shroh@snu.ac.kr.
Wah ChiuDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; SSRL, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA. Electronic address: wahc@stanford.edu.
Judith FrydmanDepartment of Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: jfrydman@stanford.edu.
Stanford University · USSeoul National University · KRETH Zurich · CHSLAC National Accelerator Laboratory · US

Funding

3 D ELECTRON MICROSCOPY OF MACROMOLECULES (5P41RR002250-27)P41GM103832 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2012 to 2019
$15.1M
Unified Data Resource for Large Complexes Determined by Cryo-Electron MicroscopyR01GM079429 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2007 to 2021
$11.6M
Mechanism of the Eukaryotic Chaperonin TRiC/CCTR01GM074074 · NIGMS · STANFORD UNIVERSITY · PI FRYDMAN, JUDITH · 2005 to 2024
$6.8M
PROTEIN FOLDING IN THE EUKARYOTIC CYTOSOLR01GM056433 · NIGMS · STANFORD UNIVERSITY · PI Judith Frydman · 1997 to 2026
$5.0M
Acquisition of a 300 kV Electron Microscope for Structural BiologyS10OD021600 · OD · STANFORD UNIVERSITY · PI CHIU, WAH · 2016 to 2016
$2.0M
NIGMS NIH HHS P41 GM103832NIGMS NIH HHS R01 GM056433NIGMS NIH HHS R01 GM074074NIGMS NIH HHS R01 GM079429NIH HHS S10 OD021600
6 · The paper itself

Abstract

The ATP-dependent ring-shaped chaperonin TRiC/CCT is essential for cellular proteostasis. To uncover why some eukaryotic proteins can only fold with TRiC assistance, we reconstituted the folding of β-tubulin using human prefoldin and TRiC. We find unstructured β-tubulin is delivered by prefoldin to the open TRiC chamber followed by ATP-dependent chamber closure. Cryo-EM resolves four near-atomic-resolution structures containing progressively folded β-tubulin intermediates within the closed TRiC chamber, culminating in native tubulin. This substrate folding pathway appears closely guided by site-specific interactions with conserved regions in the TRiC chamber. Initial electrostatic interactions between the TRiC interior wall and both the folded tubulin N domain and its C-terminal E-hook tail establish the native substrate topology, thus enabling C-domain folding. Intrinsically disordered CCT C termini within the chamber promote subsequent folding of tubulin's core and middle domains and GTP-binding. Thus, TRiC's chamber provides chemical and topological directives that shape the folding landscape of its obligate substrates.

Indexed as

Chaperonin Containing TCP-1TubulinAdenosine TriphosphateHumansProtein FoldingProteostasisAdenosine TriphosphateChaperonin Containing TCP-1Tubulinchaperonechaperonincryo-EMprefoldinTRiC/CCTtubulinXL-MS

Identifiers

PMID36493755
PMCPMC9735246
OpenAlexW4312019583

What OpenQuestion holds

Textmetadata
LicenceTDM
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.