Evidence map›Paper›PMID 24711386›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

The structured core domain of αB-crystallin can prevent amyloid fibrillation and associated toxicity.

Georg K A Hochberg, Heath Ecroyd, Cong Liu, Dezerae Cox, Duilio Cascio, Michael R Sawaya, Miranda P Collier, James Stroud, John A Carver, Andrew J Baldwin and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
9.8field-weighted citation impact, top 1% 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

118 citing papers in PubMed, 217 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Aquaporin-0-protein interactions elucidated by crosslinking mass spectrometry.Biochemical and biophysical research communications · 2024
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Dissecting the Self-assembly Dynamics of Imperfect Repeats in α-Synuclein.Journal of chemical information and modeling · 2023
    Article
  20. Article

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

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

14 authors at 5 institutions in 3 countries.

Georg K A HochbergPhysical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom.
Heath Ecroyd
Cong Liu
Dezerae Cox
Duilio Cascio
Michael R Sawaya
Miranda P Collier
James Stroud
John A Carver
Andrew J Baldwin
Carol V Robinson
David S Eisenberg
Justin L P Benesch
Arthur Laganowsky
University of Oxford · GBUniversity of California, Los Angeles · USUniversity of Wollongong · AUAustralian National University · AUHoward Hughes Medical Institute · US

Funding

Structural Biology of Amyloid DiseaseR01AG029430 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EISENBERG, DAVID · 2007 to 2016
$3.9M
Biotechnology and Biological Sciences Research CouncilHoward Hughes Medical InstituteNIA NIH HHS AG029430NIA NIH HHS R01 AG029430
6 · The paper itself

Abstract

Mammalian small heat-shock proteins (sHSPs) are molecular chaperones that form polydisperse and dynamic complexes with target proteins, serving as a first line of defense in preventing their aggregation into either amorphous deposits or amyloid fibrils. Their apparently broad target specificity makes sHSPs attractive for investigating ways to tackle disorders of protein aggregation. The two most abundant sHSPs in human tissue are αB-crystallin (ABC) and HSP27; here we present high-resolution structures of their core domains (cABC, cHSP27), each in complex with a segment of their respective C-terminal regions. We find that both truncated proteins dimerize, and although this interface is labile in the case of cABC, in cHSP27 the dimer can be cross-linked by an intermonomer disulfide linkage. Using cHSP27 as a template, we have designed an equivalently locked cABC to enable us to investigate the functional role played by oligomerization, disordered N and C termini, subunit exchange, and variable dimer interfaces in ABC. We have assayed the ability of the different forms of ABC to prevent protein aggregation in vitro. Remarkably, we find that cABC has chaperone activity comparable to that of the full-length protein, even when monomer dissociation is restricted through disulfide linkage. Furthermore, cABC is a potent inhibitor of amyloid fibril formation and, by slowing the rate of its aggregation, effectively reduces the toxicity of amyloid-β peptide to cells. Overall we present a small chaperone unit together with its atomic coordinates that potentially enables the rational design of more effective chaperones and amyloid inhibitors.

Indexed as

alpha-Crystallin B ChainAmino Acid SequenceAmyloid beta-PeptidesAnimalsCrystallizationCysteineHEK293 CellsHeLa CellsHSP27 Heat-Shock ProteinsHumansMagnetic Resonance SpectroscopyMammalsMolecular Sequence DataPC12 CellsProtein MultimerizationProtein Structure, Quaternaryalpha-Crystallin B ChainAmyloid beta-PeptidesCysteineHSP27 Heat-Shock Proteinsion mobility mass spectrometrynuclear magnetic resonance spectroscopyX-ray crystallography

Identifiers

PMID24711386
PMCPMC4000792
OpenAlexW2086910133

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.