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| | ==Solution structure of the N-terminal domain of human FKBP38 (FKBP38NTD)== | | ==Solution structure of the N-terminal domain of human FKBP38 (FKBP38NTD)== |
| - | <StructureSection load='2mf9' size='340' side='right'caption='[[2mf9]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mf9' size='340' side='right'caption='[[2mf9]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mf9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2jwx 2jwx]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MF9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mf9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2jwx 2jwx]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MF9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP8, FKBP38 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2mf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mf9 OCA], [https://pdbe.org/2mf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mf9 RCSB], [https://www.ebi.ac.uk/pdbsum/2mf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mf9 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://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=2mf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mf9 OCA], [https://pdbe.org/2mf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mf9 RCSB], [https://www.ebi.ac.uk/pdbsum/2mf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mf9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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/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;"> | | <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: Kang C]] |
| - | [[Category: Kang, C]] | + | [[Category: Sattler M]] |
| - | [[Category: Sattler, M]] | + | [[Category: Simon B]] |
| - | [[Category: Simon, B]] | + | [[Category: Ye H]] |
| - | [[Category: Ye, H]] | + | [[Category: Yoon HS]] |
| - | [[Category: Yoon, H S]] | + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Central helix]]
| + | |
| - | [[Category: Flexible n-terminal extension]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| Structural highlights
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
FKBP38 regulates apoptosis through unique interactions with multiple regulators including Bcl-2. Interestingly, the peptidylprolyl isomerase activity of FKBP38 is only detectable when it binds to calcium-saturated calmodulin (CaM/Ca(2+)). This, in turn, permits the formation of a complex with Bcl-2. FKBP38 thereby provides an important link between isomerase activity and apoptotic pathways. Here, we show that the N-terminal extension (residues 1-32) preceding the catalytic domain of FKBP38 has an autoinhibitory activity. The core isomerase activity of FKBP38 is inhibited by transient interactions involving the flexible N-terminal extension that precedes the catalytic domain. Notably, CaM/Ca(2+) binds to this N-terminal extension and thereby releases the autoinhibitory contacts between the N-terminal extension and the catalytic domain, thus potentiating the isomerase activity of FKBP38. Our data demonstrate how CaM/Ca(2+) modulates the catalytic activity of FKBP38.
Functional role of the flexible N-terminal extension of FKBP38 in catalysis.,Kang C, Ye H, Chia J, Choi BH, Dhe-Paganon S, Simon B, Schutz U, Sattler M, Yoon HS Sci Rep. 2013 Oct 22;3:2985. doi: 10.1038/srep02985. PMID:24145868[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Kang C, Ye H, Chia J, Choi BH, Dhe-Paganon S, Simon B, Schutz U, Sattler M, Yoon HS. Functional role of the flexible N-terminal extension of FKBP38 in catalysis. Sci Rep. 2013 Oct 22;3:2985. doi: 10.1038/srep02985. PMID:24145868 doi:http://dx.doi.org/10.1038/srep02985
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