TY - JOUR
T1 - The known unknowns of the Hsp90 chaperone
AU - Silbermann, Laura-Marie
AU - Vermeer, Benjamin
AU - Schmid, Sonja
AU - Tych, Katarzyna
N1 - © 2024, Silbermann, Vermeer et al.
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 Heat-Shock Proteins/metabolism
KW - Humans
KW - Protein Folding
KW - Molecular Chaperones/metabolism
KW - Proteostasis
KW - Animals
U2 - 10.7554/eLife.102666
DO - 10.7554/eLife.102666
M3 - Review article
C2 - 39737863
SN - 2050-084X
VL - 13
JO - eLife
JF - eLife
M1 - e102666
ER -