Evidence map›Paper›PMID 36266349›Full record

ArticleNature chemical biology2023

A fluorescent multi-domain protein reveals the unfolding mechanism of Hsp70.

Satyam Tiwari, Bruno Fauvet, Salvatore Assenza, Paolo De Los Rios, Pierre Goloubinoff

Erratum issuedAbstract read
In one paragraph

Article in Nature chemical biology, 2023. 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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
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  4. Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Satyam TiwariDepartment of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Bruno FauvetInstitute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne - EPFL, Lausanne, Switzerland.
Salvatore AssenzaDepartamento de Física Teórica de la Materia Condensada, Universidad Autónoma de Madrid, Madrid, Spain.ORCID 0000-0001-9983-8927
Paolo De Los RiosInstitute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne - EPFL, Lausanne, Switzerland. paolo.delosrios@epfl.ch.ORCID 0000-0002-5394-5062
Pierre GoloubinoffDepartment of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. pierre.goloubinoff@unil.ch.ORCID 0000-0002-4802-0807

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Detailed understanding of the mechanism by which Hsp70 chaperones protect cells against protein aggregation is hampered by the lack of a comprehensive characterization of the aggregates, which are typically heterogeneous. Here we designed a reporter chaperone substrate, MLucV, composed of a stress-labile luciferase flanked by stress-resistant fluorescent domains, which upon denaturation formed a discrete population of small aggregates. Combining Förster resonance energy transfer and enzymatic activity measurements provided unprecedented details on the aggregated, unfolded, Hsp70-bound and native MLucV conformations. The Hsp70 mechanism first involved ATP-fueled disaggregation and unfolding of the stable pre-aggregated substrate, which stretched MLucV beyond simply unfolded conformations, followed by native refolding. The ATP-fueled unfolding and refolding action of Hsp70 on MLucV aggregates could accumulate native MLucV species under elevated denaturing temperatures highly adverse to the native state. These results unambiguously exclude binding and preventing of aggregation from the non-equilibrium mechanism by which Hsp70 converts stable aggregates into metastable native proteins.

Indexed as

HSP70 Heat-Shock ProteinsProtein FoldingAdenosine TriphosphateLuciferasesMolecular ChaperonesProtein DenaturationProtein UnfoldingAdenosine TriphosphateHSP70 Heat-Shock ProteinsLuciferasesMolecular Chaperones

Identifiers

PMID36266349
PMCPMC9889267

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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.