@article{fe4d1d8858af426c9ce7d761f99437b0,
title = "The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions",
abstract = "Molecular chaperones govern proteome health to support cell homeostasis. An essential eukaryotic component of the chaperone system is Hsp90. Using a chemical-biology approach, we characterized the features driving the Hsp90 physical interactome. We found that Hsp90 associated with ∼20% of the yeast proteome using its three domains to preferentially target intrinsically disordered regions (IDRs) of client proteins. Hsp90 selectively utilized an IDR to regulate client activity as well as maintained IDR-protein health by preventing the transition to stress granules or P-bodies at physiological temperatures. We also discovered that Hsp90 controls the fidelity of ribosome initiation that triggers a heat shock response when disrupted. Our study provides insights into how this abundant molecular chaperone supports a dynamic and healthy native protein landscape.",
keywords = "Hsp90, fidelity of translation initiation, intrinsically disordered regions, molecular chaperone, proteostasis",
author = "Kolhe, {Janhavi A.} and Babu, {Neethu L.} and Freeman, {Brian C.}",
note = "We are grateful to Anna Mankovich (UIUC), Dr. Matthias Mayer (U. Heidleberg), and Dr. Titus Franzmann (T.U. Dresden) for their technical help with experimental approaches. We thank Dr. Maya Schuldiner (Weizmann Institute of Science) for her kind gift of the amino-terminal GFP fusion library, Dr. Jon Lorsch (NIH) for his generous gift of the dual luciferase system, and Dr. Alex Campos (Sanford Burnham Prebys) with the mass spectrometry analysis. This work was funded by NIH R35 GM136660 . We are grateful to Anna Mankovich (UIUC), Dr. Matthias Mayer (U. Heidleberg), and Dr. Titus Franzmann (T.U. Dresden) for their technical help with experimental approaches. We thank Dr. Maya Schuldiner (Weizmann Institute of Science) for her kind gift of the amino-terminal GFP fusion library, Dr. Jon Lorsch (NIH) for his generous gift of the dual luciferase system, and Dr. Alex Campos (Sanford Burnham Prebys) with the mass spectrometry analysis. This work was funded by NIH R35 GM136660. J.A.K. designed the research, performed the research, analyzed the data, and wrote the paper; N.L.B. performed the research; B.C.F. designed the research, performed the research, analyzed the data, wrote the paper, and secured funding. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.",
year = "2023",
month = jun,
day = "15",
doi = "10.1016/j.molcel.2023.05.021",
language = "English (US)",
volume = "83",
pages = "2035--2044.e7",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "12",
}