Evidence map›Paper›PMID 29979963›Full record

ArticleMolecular cell2018

Quantifying Nucleation In Vivo Reveals the Physical Basis of Prion-like Phase Behavior.

Tarique Khan, Tejbir S Kandola, Jianzheng Wu, Shriram Venkatesan, Ellen Ketter, Jeffrey J Lange, Alejandro Rodríguez Gama, Andrew Box, Jay R Unruh, Malcolm Cook and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Molecular cell, 2018. 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 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing 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

62 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. A tool to dissect heterotypic determinants of homotypic protein phase behavior.Protein science : a publication of the Protein Society · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. A tunable affinity fusion tag for protein self-assembly.bioRxiv : the preprint server for biology · 2025
    Article
  13. Functional constraints ofbioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Article
  16. Aclarubicin Reduces the Nuclear Mobility of Human DNA Topoisomerase IIβ.International journal of molecular sciences · 2024
    Article
  17. Article
  18. Mapping of Prion Structures in the Yeast Rnq1.International journal of molecular sciences · 2024
    Article
  19. Article
  20. Analysis of Phase Separation of EARLY FLOWERING 3.Methods in molecular biology (Clifton, N.J.) · 2024
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Tarique KhanStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Tejbir S KandolaStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Jianzheng WuStowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Shriram VenkatesanStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Ellen KetterStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Jeffrey J LangeStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Alejandro Rodríguez GamaStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Andrew BoxStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Jay R UnruhStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Malcolm CookStowers Institute for Medical Research, Kansas City, MO 64110, USA.
Randal HalfmannStowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: rhn@stowers.org.

Funding

University of Kansas Alzheimer's Disease Research Center (KU ADRC)P30AG072973 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Jaime Perales Puchalt · 2021 to 2026
$25.3M
University of Kansas Alzheimer's Disease Core CentersP30AG035982 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI SWERDLOW, RUSSELL H. · 2011 to 2020
$16.6M
Contributions of protein aggregation to gene regulation and phenotypic diversityDP5OD009152 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI HALFMANN, RANDAL ARTHUR · 2011 to 2015
$1.6M
NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG072973NIH HHS DP5 OD009152
6 · The paper itself

Abstract

Protein self-assemblies modulate protein activities over biological timescales that can exceed the lifetimes of the proteins or even the cells that harbor them. We hypothesized that these timescales relate to kinetic barriers inherent to the nucleation of ordered phases. To investigate nucleation barriers in living cells, we developed distributed amphifluoric FRET (DAmFRET). DAmFRET exploits a photoconvertible fluorophore, heterogeneous expression, and large cell numbers to quantify via flow cytometry the extent of a protein's self-assembly as a function of cellular concentration. We show that kinetic barriers limit the nucleation of ordered self-assemblies and that the persistence of the barriers with respect to concentration relates to structure. Supersaturation resulting from sequence-encoded nucleation barriers gave rise to prion behavior and enabled a prion-forming protein, Sup35 PrD, to partition into dynamic intracellular condensates or to form toxic aggregates. Our results suggest that nucleation barriers govern cytoplasmic inheritance, subcellular organization, and proteotoxicity.

Indexed as

Protein AggregatesFlow CytometryPeptide Termination FactorsPrion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsPeptide Termination FactorsPrion ProteinsProtein AggregatesSaccharomyces cerevisiae ProteinsSUP35 protein, S cerevisiaeamyloidDAmFRETlow-complexity sequencesnucleation barrierphase transitionphotoswitchableprionsprotein aggregationproteotoxicitysupersaturation

Identifiers

PMID29979963
PMCPMC6086602

What OpenQuestion holds

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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.