Evidence map›Paper›PMID 37069154›Full record

ArticleNature communications2023

Hsp90 provides a platform for kinase dephosphorylation by PP5.

Maru Jaime-Garza, Carlos A Nowotny, Daniel Coutandin, Feng Wang, Mariano Tabios, David A Agard

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

22 citing papers in PubMed, 45 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Maru Jaime-GarzaDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94143, USA.
Carlos A NowotnyDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94143, USA.ORCID 0000-0002-1260-0279
Daniel CoutandinNovartis Institutes for BioMedical Research, San Diego, CA, 92121, USA.
Feng WangDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94143, USA.
Mariano TabiosDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94143, USA.
David A AgardDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, 94143, USA. agard@msg.ucsf.edu.ORCID 0000-0003-3512-695X
University of California, San Francisco · USGenomics Institute of the Novartis Research Foundation · US

Funding

STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Structure & Mechanism: microtubule nucleation, centrosomes, phage cytoskeletonR35GM118099 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGARD, DAVID A. · 2016 to 2022
$3.6M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
NIGMS NIH HHS R35 GM118099NIGMS NIH HHS R35GM118099NIGMS NIH HHS T32 GM008284NIH HHS 1S10OD020054NIH HHS 1S10OD021741NIH HHS 1S10OD026881NIH HHS S10 OD020054NIH HHS S10 OD021741NIH HHS S10 OD026881
6 · The paper itself

Abstract

The Hsp90 molecular chaperone collaborates with the phosphorylated Cdc37 cochaperone for the folding and activation of its many client kinases. As with many kinases, the Hsp90 client kinase CRaf is activated by phosphorylation at specific regulatory sites. The cochaperone phosphatase PP5 dephosphorylates CRaf and Cdc37 in an Hsp90-dependent manner. Although dephosphorylating Cdc37 has been proposed as a mechanism for releasing Hsp90-bound kinases, here we show that Hsp90 bound kinases sterically inhibit Cdc37 dephosphorylation indicating kinase release must occur before Cdc37 dephosphorylation. Our cryo-EM structure of PP5 in complex with Hsp90:Cdc37:CRaf reveals how Hsp90 both activates PP5 and scaffolds its association with the bound CRaf to dephosphorylate phosphorylation sites neighboring the kinase domain. Thus, we directly show how Hsp90's role in maintaining protein homeostasis goes beyond folding and activation to include post translationally modifying its client kinases.

Indexed as

Cell Cycle ProteinsHSP90 Heat-Shock ProteinsGlycoproteinsHumansMolecular ChaperonesProtein BindingCell Cycle ProteinsGlycoproteinsHSP90 Heat-Shock ProteinsMolecular Chaperonestissue-factor-pathway inhibitor 2

Identifiers

PMID37069154
PMCPMC10110553
OpenAlexW4366085473

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.