Evidence map›Paper›PMID 39922190›Full record

ArticleCell chemical biology2025

De novo designed Hsp70 activator dissolves intracellular condensates.

Jason Z Zhang, Nathan Greenwood, Jason Hernandez, Josh T Cuperus, Buwei Huang, Bryan D Ryder, Christine Queitsch, Jason E Gestwicki, David Baker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
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  7. Article
  8. Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026
    Review
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  10. Article
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4 · The record

Corrections and comments

  • Update of
    2023
5 · Who and what money

Authors and funding

9 authors.

Jason Z ZhangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: jzz0428@uw.edu.
Nathan GreenwoodDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jason HernandezInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA.
Josh T CuperusDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Buwei HuangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Bryan D RyderInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA.
Christine QueitschDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
Jason E GestwickiInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dabaker@uw.edu.

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
Molecular Chaperones and Small MoleculesR01NS059690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason E Gestwicki · 2008 to 2026
$7.9M
Understanding gene regulation in contextR35GM139532 · NIGMS · UNIVERSITY OF WASHINGTON · PI Christine Queitsch · 2021 to 2026
$3.3M
NHGRI NIH HHS RM1 HG010461NIGMS NIH HHS R35 GM139532NINDS NIH HHS R01 NS059690
6 · The paper itself

Abstract

Protein quality control (PQC) is carried out in part by the chaperone Hsp70 in concert with adapters of the J-domain protein (JDP) family. The JDPs, also called Hsp40s, are thought to recruit Hsp70 into complexes with specific client proteins. However, the molecular principles regulating this process are not well understood. We describe the de novo design of Hsp70 binding proteins that either inhibit or stimulate Hsp70 ATPase activity. An ATPase stimulating design promoted the refolding of denatured luciferase in vitro, similar to native JDPs. Targeting of this design to intracellular condensates resulted in their nearly complete dissolution and revealed roles as cell growth promoting signaling hubs. The designs inform our understanding of chaperone structure-function relationships and provide a general and modular way to target PQC systems to regulate condensates and other cellular targets.

Indexed as

HSP40 Heat-Shock ProteinsHSP70 Heat-Shock ProteinsAdenosine TriphosphatasesHumansAdenosine TriphosphatasesHSP40 Heat-Shock ProteinsHSP70 Heat-Shock ProteinschaperonescondensatesHsp70protein design

Identifiers

PMID39922190
PMCPMC11928274

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.