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PDBsum entry 1iip
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Two structures of cyclophilin 40: folding and fidelity in the tpr domains.
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Authors
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P.Taylor,
J.Dornan,
A.Carrello,
R.F.Minchin,
T.Ratajczak,
M.D.Walkinshaw.
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Ref.
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Structure, 2001,
9,
431-438.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 5.
Figure 5. Stereo Picture of the Main Intermolecular
Interaction in the Tetragonal Form of Cyp40 and an Overlay of
the Folding Intermediate Dimer and the Fully Folded Conformer(a)
The partially unfolded TPR domains form a symmetrical dimer. One
molecule is colored as in Figure 3b, and the partner molecule is
colored red. The first TPR, comprising helices P and Q (shown in
the boxed region), make an intermolecular contact with helix R'
of the dimer-related molecule.(b) The boxed region of (b), with
the same color scheme, showing helices P, Q, and R' for the
tetragonal form, overlaid with helices P, Q, and R (yellow) of
the folded TPR domain of the monoclinic form. The intra- and
intermolecular interactions of helix R with helices P and Q are
seen to be nearly identical
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
431-438)
copyright 2001.
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