5mgx | pdb_00005mgx
The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90
Structural highlights
Function[FKBP8_HUMAN] Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis.[1] [2] [3] Publication Abstract from PubMedTetratricopeptide (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. The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90.,Blundell KL, Pal M, Roe SM, Pearl LH, Prodromou C PLoS One. 2017 Mar 9;12(3):e0173543. doi: 10.1371/journal.pone.0173543., eCollection 2017. PMID:28278223[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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