1iip
From Proteopedia
(New page: 200px<br /><applet load="1iip" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iip, resolution 2.00Å" /> '''Bovine Cyclophilin 4...) |
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| - | [[Image:1iip.jpg|left|200px]]<br /><applet load="1iip" size=" | + | [[Image:1iip.jpg|left|200px]]<br /><applet load="1iip" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1iip, resolution 2.00Å" /> | caption="1iip, resolution 2.00Å" /> | ||
'''Bovine Cyclophilin 40, Tetragonal Form'''<br /> | '''Bovine Cyclophilin 40, Tetragonal Form'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The "large immunophilin" family consists of domains of | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1IIP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http:// | + | 1IIP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IIP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Carrello, A.]] | [[Category: Carrello, A.]] | ||
[[Category: Dornan, J.]] | [[Category: Dornan, J.]] | ||
| - | [[Category: Minchin, R | + | [[Category: Minchin, R F.]] |
[[Category: Ratajczak, T.]] | [[Category: Ratajczak, T.]] | ||
[[Category: Taylor, P.]] | [[Category: Taylor, P.]] | ||
| - | [[Category: Walkinshaw, M | + | [[Category: Walkinshaw, M D.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: ppiase immunophilin tetratricopeptide]] | [[Category: ppiase immunophilin tetratricopeptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:12:18 2008'' |
Revision as of 11:12, 21 February 2008
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Bovine Cyclophilin 40, Tetragonal Form
Overview
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.
About this Structure
1IIP is a Single protein structure of sequence from Bos taurus with as ligand. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.
Reference
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
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