Structural highlights
Function
[PPID_BOVIN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co-chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA-binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity. Involved in regulation of UV radiation-induced apoptosis.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Two structures of cyclophilin 40: folding and fidelity in the TPR domains.,Taylor P, Dornan J, Carrello A, Minchin RF, Ratajczak T, Walkinshaw MD Structure. 2001 May 9;9(5):431-8. PMID:11377203[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kieffer LJ, Thalhammer T, Handschumacher RE. Isolation and characterization of a 40-kDa cyclophilin-related protein. J Biol Chem. 1992 Mar 15;267(8):5503-7. PMID:1544925
- ↑ Mok D, Allan RK, Carrello A, Wangoo K, Walkinshaw MD, Ratajczak T. The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains. FEBS Lett. 2006 May 15;580(11):2761-8. Epub 2006 Apr 24. PMID:16650407 doi:http://dx.doi.org/10.1016/j.febslet.2006.04.039
- ↑ Taylor P, Dornan J, Carrello A, Minchin RF, Ratajczak T, Walkinshaw MD. Two structures of cyclophilin 40: folding and fidelity in the TPR domains. Structure. 2001 May 9;9(5):431-8. PMID:11377203
