The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90

Blundell, Katie L I M, Pal, Mohinder, Roe, S Mark, Pearl, Laurence H and Prodromou, Chrisostomos (2017) The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90. PLoS ONE, 12 (3). e0173543. ISSN 1932-6203

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Abstract

Tetratricopeptide (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.

Item Type: Article
Keywords: Hso90, FKBP38, FKBP8, chaperone, co-chaperone
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QP Physiology > QP0501 Animal biochemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Chrisostomos Prodromou
Date Deposited: 10 Mar 2017 14:53
Last Modified: 10 Mar 2017 14:59
URI: http://sro.sussex.ac.uk/id/eprint/67055

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Project NameSussex Project NumberFunderFunder Ref
Mechanisms of client protein activation and regulation by the Hsp90 molecular chaperone systemG0662WELLCOME TRUST095605/Z11/Z