8auw
From Proteopedia
(Difference between revisions)
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- | ==Cryo-EM structure of human BIRC6 in complex with SMAC== | + | ==Cryo-EM structure of human BIRC6 in complex with SMAC.== |
<StructureSection load='8auw' size='340' side='right'caption='[[8auw]], [[Resolution|resolution]] 7.20Å' scene=''> | <StructureSection load='8auw' size='340' side='right'caption='[[8auw]], [[Resolution|resolution]] 7.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8auw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AUW FirstGlance]. <br> | <table><tr><td colspan='2'>[[8auw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AUW FirstGlance]. <br> | ||
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.2Å</td></tr> |
+ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8auw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8auw OCA], [https://pdbe.org/8auw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8auw RCSB], [https://www.ebi.ac.uk/pdbsum/8auw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8auw ProSAT]</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=8auw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8auw OCA], [https://pdbe.org/8auw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8auw RCSB], [https://www.ebi.ac.uk/pdbsum/8auw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8auw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/BIRC6_HUMAN BIRC6_HUMAN] Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its tragets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification.<ref>PMID:14765125</ref> <ref>PMID:15200957</ref> <ref>PMID:18329369</ref> | [https://www.uniprot.org/uniprot/BIRC6_HUMAN BIRC6_HUMAN] Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its tragets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification.<ref>PMID:14765125</ref> <ref>PMID:15200957</ref> <ref>PMID:18329369</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers. | ||
+ | |||
+ | Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.,Ehrmann JF, Grabarczyk DB, Heinke M, Deszcz L, Kurzbauer R, Hudecz O, Shulkina A, Gogova R, Meinhart A, Versteeg GA, Clausen T Science. 2023 Mar 17;379(6637):1117-1123. doi: 10.1126/science.ade8873. Epub 2023 , Feb 9. PMID:36758105<ref>PMID:36758105</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 8auw" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> |
Current revision
Cryo-EM structure of human BIRC6 in complex with SMAC.
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