journal.pone.0173543.pdf (1.71 MB)
The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90
journal contribution
posted on 2023-06-09, 05:26 authored by Katie L I M Blundell, Mohinder Pal, S Mark Roe, Laurence PearlLaurence Pearl, Chrisostomos ProdromouChrisostomos ProdromouTetratricopeptide (TPR) domains are known protein interaction domains. We show that the TPR domain of FKBP8 selectively binds Hsp90, and interactions upstream of the conserved MEEVD motif are critical for tight binding. In contrast FKBP8 failed to bind intact Hsp70. The PPIase domain was not essential for the interaction with Hsp90 and binding was completely encompassed by the TPR domain alone. The conformation adopted by Hsp90 peptides, containing the conserved MEEVD motif, in the crystal structure were similar to that seen for the TPR domains of CHIP, AIP and Tah1. The carboxylate clamp interactions with bound Hsp90 peptide were a critical component of the interaction and mutation of Lys 307, involved in the carboxylate clamp, completely disrupted the interaction with Hsp90. FKBP8 binding to Hsp90 did not substantially influence its ATPase activity.
Funding
Mechanisms of client protein activation and regulation by the Hsp90 molecular chaperone system; G0662; WELLCOME TRUST; 095605/Z11/Z
History
Publication status
- Published
File Version
- Published version
Journal
PLoS ONEISSN
1932-6203Publisher
Public Library of ScienceExternal DOI
Issue
3Volume
12Article number
e0173543Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-03-10First Open Access (FOA) Date
2017-03-10First Compliant Deposit (FCD) Date
2017-03-10Usage metrics
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