Two structures of cyclophilin 40: Folding and fidelity in the TPR domains

Taylor, Paul, Dornan, Jacqueline, Carrello, Amerigo, Minchin, Rodney F., Ratajczak, Thomas and Walkinshaw, Malcolm D. (2001) Two structures of cyclophilin 40: Folding and fidelity in the TPR domains. Structure, 9 5: 431-438. doi:10.1016/S0969-2126(01)00603-7


Author Taylor, Paul
Dornan, Jacqueline
Carrello, Amerigo
Minchin, Rodney F.
Ratajczak, Thomas
Walkinshaw, Malcolm D.
Title Two structures of cyclophilin 40: Folding and fidelity in the TPR domains
Journal name Structure   Check publisher's open access policy
ISSN 0969-2126
Publication date 2001
Sub-type Article (original research)
DOI 10.1016/S0969-2126(01)00603-7
Volume 9
Issue 5
Start page 431
End page 438
Total pages 8
Place of publication Cambridge
Publisher Cell Press
Language eng
Subject 06 Biological Sciences
Formatted abstract
Background: The “large immunophilin” family consists of domains of cyclophilin or FK506 binding protein linked to a tetratricopeptide (TPR) domain. They are intimately associated with steroid receptor complexes and bind to the C-terminal domain of Hsp90 via the TPR domain. The competitive binding of specific large immunophilins and other TPR-Hsp90 proteins provides a regulatory mechanism for Hsp90 chaperone activity.

Results: We have solved the X-ray structures of monoclinic and tetragonal forms of Cyp40. In the monoclinic form, the TPR domain consists of seven helices of variable length incorporating three TPR motifs, which provide a convincing binding surface for the Hsp90 C-terminal MEEVD sequence. The C-terminal residues of Cyp40 protrude out beyond the body of the TPR domain to form a charged helix—the putative calmodulin binding site. However, in the tetragonal form, two of the TPR helices have straightened out to form one extended helix, providing a dramatically different conformation of the molecule.

Conclusions:
The X-ray structures are consistent with the role of Cyclophilin 40 as a multifunctional signaling protein involved in a variety of protein-protein interactions. The intermolecular helix-helix interactions in the tetragonal form mimic the intramolecular interactions found in the fully folded monoclinic form. These conserved intra- and intermolecular TPR-TPR interactions are illustrative of a high-fidelity recognition mechanism. The two structures also open up the possibility that partially folded forms of TPR may be important in domain swapping and protein recognition.
Keyword Biochemistry & Molecular Biology
Biophysics
Cell Biology
Cyclophilin
Hsp90
Immunophilin
Tetratricopeptide Repeat
Tpr
Protein Recognition
Tetratricopeptide Repeat Domain
Saccharomyces-cerevisiae
Escherichia-coli
Binding Domain
Shock Protein
Receptor
Calmodulin
Cloning
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Mon, 13 Aug 2007, 12:19:45 EST