View source for 5wve


==Apaf-1-Caspase-9 holoenzyme==
<SX load='5wve' size='340' side='right' viewer='molstar' caption='[[5wve]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wve]] is a 25 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WVE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5wve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wve OCA], [https://pdbe.org/5wve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wve RCSB], [https://www.ebi.ac.uk/pdbsum/5wve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wve ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/APAF_HUMAN APAF_HUMAN] Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.<ref>PMID:10393175</ref> <ref>PMID:12804598</ref> 
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== Publication Abstract from PubMed ==
Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme. The molecular mechanism of caspase-9 activation remains largely enigmatic. Here, we report the cryoelectron microscopy (cryo-EM) structure of an apoptotic holoenzyme and structure-guided biochemical analyses. The caspase recruitment domains (CARDs) of Apaf-1 and caspase-9 assemble in two different ways: a 4:4 complex docks onto the central hub of the apoptosome, and a 2:1 complex binds the periphery of the central hub. The interface between the CARD complex and the central hub is required for caspase-9 activation within the holoenzyme. Unexpectedly, the CARD of free caspase-9 strongly inhibits its proteolytic activity. These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain.

Mechanistic insights into caspase-9 activation by the structure of the apoptosome holoenzyme.,Li Y, Zhou M, Hu Q, Bai XC, Huang W, Scheres SH, Shi Y Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1542-1547. doi:, 10.1073/pnas.1620626114. Epub 2017 Jan 31. PMID:28143931<ref>PMID:28143931</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5wve" style="background-color:#fffaf0;"></div>

==See Also==
*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
*[[Caspase 3D structures|Caspase 3D structures]]
*[[Cytochrome C 3D structures|Cytochrome C 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Equus caballus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hu Q]]
[[Category: Li Y]]
[[Category: Shi Y]]
[[Category: Zhou M]]