5MGX

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

Summary for 5MGX

• Entry DOI: 10.2210/pdb5mgx/pdb
• Descriptor: yeast HSP90 C-terminus, Peptidyl-prolyl cis-trans isomerase FKBP8 (3 entities in total)
• Functional Keywords: hsp90, ppiase, teratricopeptide, immunophilin, isomerase
• Biological source: Homo sapiens (Human); More
• Cellular location: Mitochondrion . Isoform 1: Mitochondrion membrane ; Single-pass membrane protein; Cytoplasmic side . Isoform 3: Mitochondrion membrane ; Single-pass membrane protein; Cytoplasmic side : Q14318
• Total number of polymer chains: 8
• Total formula weight: 131086.60

Authors

Roe, S.M.,Blundell, K.L.,Prodromou, C. (deposition date: 2016-11-22, release date: 2017-03-22, Last modification date: 2024-01-17)

Primary citation

Blundell, K.L.,Pal, M.,Roe, S.M.,Pearl, L.H.,Prodromou, C.
The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90.
PLoS ONE, 12:e0173543-e0173543, 2017

PubMed 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.

PubMed: 28278223
DOI: 10.1371/journal.pone.0173543

Experimental method

X-RAY DIFFRACTION (2.18 Å)