5mgx

From Proteopedia

(Difference between revisions)

Revision as of 16:09, 22 March 2017

The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90

Structural highlights

5mgx is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Peptidylprolyl isomerase, with EC number 5.2.1.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FKBP8_HUMAN] Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Tetratricopeptide (TPR) domains are known protein interaction domains. We show that the TPR domain of FKBP8 selectively binds Hsp90, and interactions upstream of the conserved MEEVD motif are critical for tight binding. In contrast FKBP8 failed to bind intact Hsp70. The PPIase domain was not essential for the interaction with Hsp90 and binding was completely encompassed by the TPR domain alone. The conformation adopted by Hsp90 peptides, containing the conserved MEEVD motif, in the crystal structure were similar to that seen for the TPR domains of CHIP, AIP and Tah1. The carboxylate clamp interactions with bound Hsp90 peptide were a critical component of the interaction and mutation of Lys 307, involved in the carboxylate clamp, completely disrupted the interaction with Hsp90. FKBP8 binding to Hsp90 did not substantially influence its ATPase activity.

The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90.,Blundell KL, Pal M, Roe SM, Pearl LH, Prodromou C PLoS One. 2017 Mar 9;12(3):e0173543. doi: 10.1371/journal.pone.0173543., eCollection 2017. PMID:28278223^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shirane M, Nakayama KI. Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis. Nat Cell Biol. 2003 Jan;5(1):28-37. PMID:12510191 doi:http://dx.doi.org/10.1038/ncb894
↑ Kang CB, Feng L, Chia J, Yoon HS. Molecular characterization of FK-506 binding protein 38 and its potential regulatory role on the anti-apoptotic protein Bcl-2. Biochem Biophys Res Commun. 2005 Nov 11;337(1):30-8. PMID:16176796 doi:http://dx.doi.org/S0006-291X(05)02012-7
↑ Weiwad M, Edlich F, Erdmann F, Jarczowski F, Kilka S, Dorn M, Pechstein A, Fischer G. A reassessment of the inhibitory capacity of human FKBP38 on calcineurin. FEBS Lett. 2005 Mar 14;579(7):1591-6. PMID:15757646 doi:http://dx.doi.org/S0014-5793(05)00180-8
↑ Blundell KL, Pal M, Roe SM, Pearl LH, Prodromou C. The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90. PLoS One. 2017 Mar 9;12(3):e0173543. doi: 10.1371/journal.pone.0173543., eCollection 2017. PMID:28278223 doi:http://dx.doi.org/10.1371/journal.pone.0173543

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mgx"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5mgx is ON HOLD
+==The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90==
+<StructureSection load='5mgx' size='340' side='right' caption='[[5mgx]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5mgx]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MGX FirstGlance]. <br>
+</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgx OCA], [http://pdbe.org/5mgx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mgx RCSB], [http://www.ebi.ac.uk/pdbsum/5mgx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgx ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/FKBP8_HUMAN FKBP8_HUMAN]] Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis.<ref>PMID:12510191</ref> <ref>PMID:16176796</ref> <ref>PMID:15757646</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Tetratricopeptide (TPR) domains are known protein interaction domains. We show that the TPR domain of FKBP8 selectively binds Hsp90, and interactions upstream of the conserved MEEVD motif are critical for tight binding. In contrast FKBP8 failed to bind intact Hsp70. The PPIase domain was not essential for the interaction with Hsp90 and binding was completely encompassed by the TPR domain alone. The conformation adopted by Hsp90 peptides, containing the conserved MEEVD motif, in the crystal structure were similar to that seen for the TPR domains of CHIP, AIP and Tah1. The carboxylate clamp interactions with bound Hsp90 peptide were a critical component of the interaction and mutation of Lys 307, involved in the carboxylate clamp, completely disrupted the interaction with Hsp90. FKBP8 binding to Hsp90 did not substantially influence its ATPase activity.
-Authors: Roe, S.M., Blundell, K.L., Prodromou, C.
+The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90.,Blundell KL, Pal M, Roe SM, Pearl LH, Prodromou C PLoS One. 2017 Mar 9;12(3):e0173543. doi: 10.1371/journal.pone.0173543., eCollection 2017. PMID:28278223<ref>PMID:28278223</ref>
-Description: The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Blundell, K.L]]
+<div class="pdbe-citations 5mgx" style="background-color:#fffaf0;"></div>
-[[Category: Roe, S.M]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Peptidylprolyl isomerase]]
+[[Category: Blundell, K L]]
 [[Category: Prodromou, C]]
+[[Category: Roe, S M]]
+[[Category: Hsp90]]
+[[Category: Immunophilin]]
+[[Category: Isomerase]]
+[[Category: Ppiase]]
+[[Category: Teratricopeptide]]

5mgx

From Proteopedia

Revision as of 16:09, 22 March 2017

The structure of FKBP38 in complex with the MEEVD tetratricopeptide binding-motif of Hsp90

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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