Two Structures of Cyclophilin 40

Taylor, Paul; Dornan, Jacqueline; Carrello, Amerigo; Minchin, Rodney F.; Ratajczak, Thomas; Walkinshaw, Malcolm D.

doi:10.1016/s0969-2126(01)00603-7

Cited by 132 publications

(64 citation statements)

References 30 publications

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“…Each single unit consists of two consecutive ␣-helices containing 12-15 residues (except ␣1 and ␣3, containing 21 and 23 residues, respectively) that cross at an angle of Ϸ20°to each other. The organizational pattern of the FKBP52 TPR domain is similar to those of FKBP51, Cyp40, PP5, and Hop (8,16,25,26). There is an additional ␣-helix (␣7) in the C terminus beyond the final TPR motif that contains the calmodulin-binding site (Fig.…”

Section: Methodsmentioning

confidence: 78%

“…In the unit cell, the pocket of molecule A faces the pocket of molecule B, and there is enough space for the peptides to fill in, but the binding pocket of molecule C is blocked by the FK2 domain of another molecule C, which explains why this molecule does not bind the peptide. Previous mutation analysis and crystal structures of TPR domains have identified residues in Hop, Cyp40, and PP5 that are essential for Hsp90 binding (8,25,26,29,30). Comparing these proteins with FKBP52, the key residues for binding Hsp90 are conserved, which suggests a functional similarity between these proteins.…”

Section: Methodsmentioning

confidence: 95%

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3D structure of human FK506-binding protein 52: Implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex

Li²,

Liu³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

154

170

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FK506-binding protein 52 (FKBP52), which binds FK506 and possesses peptidylprolyl isomerase activity, is an important immunophilin involved in the heterocomplex of steroid receptors with heat-shock protein 90. Here we report the crystal structures of two overlapped fragments [N(1-260) and C(145-459)] of FKBP52 and the complex with a C-terminal pentapeptide from heat-shock protein 90. Based on the structures of these two overlapped fragments, the complete putative structure of FKBP52 can be defined. The structure of FKBP52 is composed of two consecutive FKBP domains, a tetratricopeptide repeat domain and a short helical domain beyond the final tetratricopeptide repeat motif. Key structural differences between FKBP52 and FKBP51, including the relative orientations of the four domains and some important residue substitutions, could account for the differential functions of FKBPs.

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Section: Methodsmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 95%

3D structure of human FK506-binding protein 52: Implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex

Li²,

Liu³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

154

170

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“…The TPR domain of FKBP51 has three repeats of the TPR motif and is structurally very similar to the Hsp90-binding domains of PP5 (36), Hop (37), and Cyp40 (38). At 21 and 25 residues, respectively, ␣1 and ␣3 are longer than the usual 12-15 residues, but ␣2 and ␣4-␣6 are within the average size for TPR helices.…”

Section: Resultsmentioning

confidence: 99%

“…The structure of the Hop TPR domains (37) shows binding in an antiparallel orientation to ␣1, ␣3, ␣5, and ␣7, which form the groove for both Hsp70 and Hsp90 fragments. The report of the Cyp40 structure (38) does not have an Hsp90 fragment bound, but instead uses the crystal packing to model Hsp90 binding, which results in a binding parallel, not antiparallel, to the direction of the helices lining the binding groove. The structure of the FKBP51 TPR domain gives no indication of the binding orientation of Hsp90.…”

Section: Resultsmentioning

confidence: 99%

Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes

Sinars

Cheung‐Flynn

Rimerman

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

232

221

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The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 Å, and squirrel monkey FKBP51, to 2.8 Å, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex.

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“…Moreover, apart from serving mere anchoring functions, TPR domains of the chaperone cofactors Hip and p60/Hop also exert regulatory functions on the ATPase activities of Hsp70 and Hsp90, respectively (11,12). The conserved architecture of the TPR fold is well established based on a number of x-ray structures of different TPR domains (13)(14)(15)(16)(17)(18). Each 34-amino acid motif forms a pair of antiparallel ␣-helices.…”

mentioning

confidence: 99%