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

DOI: 10.1371/journal.pone.0173543

Authors: Katie L. I. M. Blundell (University of Sussex) , Mohinder Pal (University of Sussex) , S. Mark Roe (University of Sussex) , Laurence H. Pearl (University of Sussex) , Chrisostomos Prodromou (University of Sussex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos One , VOL 12

State: Published (Approved)
Published: March 2017
Diamond Proposal Number(s): 10088

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.

Journal Keywords: Crystal structure; Protein domains; Adenosine triphosphatase; Peptides; Glutamate; Protein interactions; Sequence motif analysis; Valine

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 14/03/2017 09:12

Documents:
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Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)