Evidence map›Paper›PMID 31160557›Full record

ArticleNature communications2019

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.

Alexandrea N Rizo, JiaBei Lin, Stephanie N Gates, Eric Tse, Stephen M Bart, Laura M Castellano, Frank DiMaio, James Shorter, Daniel R Southworth

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing 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

69 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. SNARE disassembly requires Sec18/NSF side loading.Nature structural & molecular biology · 2025
    Article
  6. SNARE disassembly requires Sec18/NSF side-loading.bioRxiv : the preprint server for biology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Big versus small: The impact of aggregate size in disease.Protein science : a publication of the Protein Society · 2023
    Review

9 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

9 authors.

Alexandrea N RizoGraduate Program in Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
JiaBei LinDepartment of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Stephanie N GatesGraduate Program in Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Eric TseDepartment of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-2082-9006
Stephen M BartDepartment of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Laura M CastellanoDepartment of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Frank DiMaioDepartment of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
James ShorterDepartment of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Daniel R SouthworthDepartment of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, 94158, USA. daniel.southworth@ucsf.edu.

Funding

Defining the mechanistic basis of a prion disaggregaseR01GM099836 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI SHORTER, JAMES · 2013 to 2024
$3.9M
Protein structure determination from low-resolution experimental dataR01GM123089 · NIGMS · UNIVERSITY OF WASHINGTON · PI DIMAIO, FRANK P · 2017 to 2025
$2.6M
Defining the conformational cycle of nitric oxide synthasesR01GM110001 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SOUTHWORTH, DANIEL RYLAND · 2015 to 2019
$1.5M
NIGMS NIH HHS R01 GM099836NIGMS NIH HHS R01 GM110001NIGMS NIH HHS R01 GM123089
6 · The paper itself

Abstract

Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) power polypeptide translocation through a central channel comprised of a hexameric spiral of protomers that contact substrate via conserved pore-loop interactions. Here we report cryo-EM structures of a hyperactive ClpB variant bound to the model substrate, casein in the presence of slowly hydrolysable ATPγS, which reveal the translocation mechanism. Distinct substrate-gripping interactions are identified for NBD1 and NBD2 pore loops. A trimer of N-terminal domains define a channel entrance that binds the polypeptide substrate adjacent to the topmost NBD1 contact. NBD conformations at the seam interface reveal how ATP hydrolysis-driven substrate disengagement and re-binding are precisely tuned to drive a directional, stepwise translocation cycle.

Indexed as

Protein TransportAAA DomainAdenosine TriphosphateCaseinsCryoelectron MicroscopyEndopeptidase ClpEscherichia coliEscherichia coli ProteinsHeat-Shock ProteinsHydrolysisModels, MolecularPeptidesProtein AggregatesProtein Subunitsadenosine 5'-O-(3-thiotriphosphate)Adenosine TriphosphateCaseinsClpB protein, E coliEndopeptidase ClpEscherichia coli ProteinsHeat-Shock ProteinsPeptidesProtein AggregatesProtein Subunits

Identifiers

PMID31160557
PMCPMC6546751

What OpenQuestion holds

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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.