The known unknowns of the Hsp90 chaperone

Laura Marie Silbermann; Benjamin Vermeer; Sonja Schmid; Katarzyna Tych

doi:10.7554/eLife.102666

The known unknowns of the Hsp90 chaperone

Laura Marie Silbermann, Benjamin Vermeer, Sonja Schmid^*, Katarzyna Tych^*

^*Corresponding author for this work

Research output: Contribution to journal › Literature review › peer-review

2 Citations (Scopus)

Abstract

Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.

Original language	English
Number of pages	21
Journal	eLife
Volume	13
DOIs	https://doi.org/10.7554/eLife.102666
Publication status	Published - 31 Dec 2024

Keywords

Hsp90
molecular biophysics
molecular chaperones
proteostasis
structural biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.7554/eLife.102666Licence: CC BY

https://edepot.wur.nl/685106Licence: CC BY

Cite this

@article{74567e69bc4e4dd9840557556e13e0a1,

title = "The known unknowns of the Hsp90 chaperone",

abstract = "Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.",

keywords = "Hsp90, molecular biophysics, molecular chaperones, proteostasis, structural biology",

author = "Silbermann, {Laura Marie} and Benjamin Vermeer and Sonja Schmid and Katarzyna Tych",

year = "2024",

month = dec,

day = "31",

doi = "10.7554/eLife.102666",

language = "English",

volume = "13",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - The known unknowns of the Hsp90 chaperone

AU - Silbermann, Laura Marie

AU - Vermeer, Benjamin

AU - Schmid, Sonja

AU - Tych, Katarzyna

PY - 2024/12/31

Y1 - 2024/12/31

N2 - Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.

AB - Molecular chaperones are vital proteins that maintain protein homeostasis by assisting in protein folding, activation, degradation, and stress protection. Among them, heat-shock protein 90 (Hsp90) stands out as an essential proteostasis hub in eukaryotes, chaperoning hundreds of 'clients' (substrates). After decades of research, several 'known unknowns' about the molecular function of Hsp90 remain unanswered, hampering rational drug design for the treatment of cancers, neurodegenerative, and other diseases. We highlight three fundamental open questions, reviewing the current state of the field for each, and discuss new opportunities, including single-molecule technologies, to answer the known unknowns of the Hsp90 chaperone.

KW - Hsp90

KW - molecular biophysics

KW - molecular chaperones

KW - proteostasis

KW - structural biology

U2 - 10.7554/eLife.102666

DO - 10.7554/eLife.102666

M3 - Literature review

C2 - 39737863

AN - SCOPUS:85214186519

SN - 2050-084X

VL - 13

JO - eLife

JF - eLife

ER -

The known unknowns of the Hsp90 chaperone

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this