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| ==Structure of Dark apoptosome in complex with Dronc CARD domain== | | ==Structure of Dark apoptosome in complex with Dronc CARD domain== |
| <StructureSection load='3j9k' size='340' side='right' caption='[[3j9k]], [[Resolution|resolution]] 4.10Å' scene=''> | | <SX load='3j9k' size='340' side='right' viewer='molstar' caption='[[3j9k]], [[Resolution|resolution]] 4.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3j9k]] is a 32 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J9K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J9K FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3j9k]] is a 32 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J9K FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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]] 4.1Å</td></tr> |
| <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3j9l|3j9l]]</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=3j9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j9k OCA], [https://pdbe.org/3j9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j9k RCSB], [https://www.ebi.ac.uk/pdbsum/3j9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j9k ProSAT]</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=3j9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3j9k RCSB], [http://www.ebi.ac.uk/pdbsum/3j9k PDBsum]</span></td></tr> | |
| </table> | | </table> |
| {{Large structure}}
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| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/ICENC_DROME ICENC_DROME]] Involved in the activation cascade of caspases responsible for apoptosis execution. Effector of steroid-mediated apoptosis during insect metamorphosis. Overexpression promotes programmed cell death. Interaction with th is required to suppress Nc-mediated cell death; via th-mediated ubiquitination of Nc. Rate-limiting caspase in rpr and W death pathway.<ref>PMID:10200258</ref> <ref>PMID:10675329</ref> <ref>PMID:10984473</ref> <ref>PMID:14517550</ref> | | [https://www.uniprot.org/uniprot/Q7KLI1_DROME Q7KLI1_DROME] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 A resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 A resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome.
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| Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila.,Pang Y, Bai XC, Yan C, Hao Q, Chen Z, Wang JW, Scheres SH, Shi Y Genes Dev. 2015 Feb 1;29(3):277-87. doi: 10.1101/gad.255877.114. PMID:25644603<ref>PMID:25644603</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| [[Category: Bai, X]] | | [[Category: Large Structures]] |
| [[Category: Chen, Z]] | | [[Category: Bai X]] |
| [[Category: Hao, Q]] | | [[Category: Chen Z]] |
| [[Category: Pang, Y]] | | [[Category: Hao Q]] |
| [[Category: Scheres, S H.W]] | | [[Category: Pang Y]] |
| [[Category: Shi, Y]] | | [[Category: Scheres SHW]] |
| [[Category: Wang, J]] | | [[Category: Shi Y]] |
| [[Category: Yan, C]] | | [[Category: Wang J]] |
| [[Category: Apoptosis]]
| | [[Category: Yan C]] |
| [[Category: Caspase activation]]
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| [[Category: Programmed cell death]]
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