Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle

Maximilian M. Biebl, Abraham Lopez, Alexandra Rehn, Lee Freiburger, Jannis Lawatscheck, Birgit Blank, Michael Sattler () and Johannes Buchner ()
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Maximilian M. Biebl: Technische Universität München
Abraham Lopez: Technische Universität München
Alexandra Rehn: Technische Universität München
Lee Freiburger: Technische Universität München
Jannis Lawatscheck: Technische Universität München
Birgit Blank: Technische Universität München
Michael Sattler: Technische Universität München
Johannes Buchner: Technische Universität München

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21063-0

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DOI: 10.1038/s41467-021-21063-0

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