Evidence map›Paper›PMID 25908822›Full record

ArticleScience (New York, N.Y.)2015

Protein folding. Translational tuning optimizes nascent protein folding in cells.

Soo Jung Kim, Jae Seok Yoon, Hideki Shishido, Zhongying Yang, LeeAnn A Rooney, Jose M Barral, William R Skach

Abstract read
PubMed Publisher
In one paragraph

Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 1 pooled it
–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

126 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
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  12. Article
  13. Article
  14. Article
  15. Translation Rates and Protein Folding.Journal of molecular biology · 2024
    Review
  16. Review
  17. Optimal design of synthetic circular RNAs.Experimental & molecular medicine · 2024
    Review
  18. Article
  19. Review
  20. Article

66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Soo Jung KimDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA.
Jae Seok YoonDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA.
Hideki ShishidoDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA.
Zhongying YangDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA.
LeeAnn A RooneyDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA.
Jose M BarralDepartment of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77550-0620, USA.
William R SkachDepartment of Biochemistry and Molecular Biology, Oregon Health and Science University (OHSU), Portland, OR 97239, USA. Cystic Fibrosis Foundation Therapeutics, Bethesda, MD 20814, USA. skachw@ohsu.edu.

Funding

Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Luiz Eduardo Bertassoni · 1997 to 2026
$60.5M
MECHANISMS OF POLYTOPIC PROTEIN BIOGENESIS IN THE ERR01GM053457 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI SKACH, WILLIAM R · 1996 to 2013
$3.5M
BIOGENESIS AND MOLECULAR PATHOGENESIS OF CFTRR01DK051818 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SKACH, WILLIAM R · 1997 to 2012
$2.9M
LTQ Orbitrap VelosS10OD012246 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVID, LARRY L · 2012 to 2012
$854k
LTQ XL Linear Ion Trap Mass SpectrometerS10RR025571 · NCRR · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVID, LARRY L · 2009 to 2009
$389k
NCI NIH HHS P30CA069533NCRR NIH HHS S10RR025571NIDDK NIH HHS R01DK51818NIGMS NIH HHS R01GM53457NIH HHS S10OD012246PHS HHS P30EYE010572
6 · The paper itself

Abstract

In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency and minimize off-pathway outcomes. However, it has been difficult to delineate experimentally the mechanisms responsible. Using fluorescence resonance energy transfer, we studied cotranslational folding of the first nucleotide-binding domain from the cystic fibrosis transmembrane conductance regulator. During synthesis, folding occurred discretely via sequential compaction of N-terminal, α-helical, and α/β-core subdomains. Moreover, the timing of these events was critical; premature α-subdomain folding prevented subsequent core formation. This process was facilitated by modulating intrinsic folding propensity in three distinct ways: delaying α-subdomain compaction, facilitating β-strand intercalation, and optimizing translation kinetics via codon usage. Thus, de novo folding is translationally tuned by an integrated cellular response that shapes the cotranslational folding landscape at critical stages of synthesis.

Indexed as

Peptide Chain Elongation, TranslationalProtein FoldingAmino Acid SequenceCodonCystic Fibrosis Transmembrane Conductance RegulatorFluorescence Resonance Energy TransferHumansKineticsMolecular Sequence DataProtein Structure, SecondaryProtein Structure, TertiaryRibosomesCodonCystic Fibrosis Transmembrane Conductance Regulator

Identifiers

What OpenQuestion holds

Textmetadata
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.