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| | <StructureSection load='5mgx' size='340' side='right'caption='[[5mgx]], [[Resolution|resolution]] 2.18Å' scene=''> | | <StructureSection load='5mgx' size='340' side='right'caption='[[5mgx]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mgx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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://proteopedia.org/fgij/fg.htm?mol=5MGX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mgx]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5MGX FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP8, FKBP38 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=5mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mgx OCA], [https://pdbe.org/5mgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mgx RCSB], [https://www.ebi.ac.uk/pdbsum/5mgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mgx ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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> | | </table> |
| | == Function == | | == 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> | + | [https://www.uniprot.org/uniprot/HSP82_YEAST HSP82_YEAST] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Required for growth at high temperatures.<ref>PMID:17114002</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Blundell, K L]] | + | [[Category: Blundell KL]] |
| - | [[Category: Prodromou, C]] | + | [[Category: Prodromou C]] |
| - | [[Category: Roe, S M]] | + | [[Category: Roe SM]] |
| - | [[Category: Hsp90]]
| + | |
| - | [[Category: Immunophilin]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Ppiase]]
| + | |
| - | [[Category: Teratricopeptide]]
| + | |
| Structural highlights
Function
HSP82_YEAST Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. The nucleotide-free form of the dimer is found in an open conformation in which the N-termini are not dimerized and the complex is ready for client protein binding. Binding of ATP induces large conformational changes, resulting in the formation of a ring-like closed structure in which the N-terminal domains associate intramolecularly with the middle domain and also dimerize with each other, stimulating their intrinsic ATPase activity and acting as a clamp on the substrate. Finally, ATP hydrolysis results in the release of the substrate. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Required for growth at high temperatures.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Proisy N, Sharp SY, Boxall K, Connelly S, Roe SM, Prodromou C, Slawin AM, Pearl LH, Workman P, Moody CJ. Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol. Chem Biol. 2006 Nov;13(11):1203-15. PMID:17114002 doi:10.1016/j.chembiol.2006.09.015
- ↑ 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
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