5wve

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'''Unreleased structure'''
 
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The entry 5wve is ON HOLD
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==Apaf-1-Caspase-9 holoenzyme==
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<StructureSection load='5wve' size='340' side='right' caption='[[5wve]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5wve]] is a 25 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WVE FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
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<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=5wve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wve OCA], [http://pdbe.org/5wve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wve RCSB], [http://www.ebi.ac.uk/pdbsum/5wve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wve ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://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> [[http://www.uniprot.org/uniprot/CYC_HORSE CYC_HORSE]] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Li, Y., Zhou, M., Hu, Q., Shi, Y.
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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>
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Description: Apaf-1-Caspase-9 holoenzyme
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 5wve" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Hu, Q]]
[[Category: Li, Y]]
[[Category: Li, Y]]
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[[Category: Zhou, M]]
 
[[Category: Shi, Y]]
[[Category: Shi, Y]]
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[[Category: Hu, Q]]
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[[Category: Zhou, M]]
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[[Category: Apoptosis]]
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[[Category: Apoptosis holoenzyme]]

Revision as of 07:08, 9 March 2017

Apaf-1-Caspase-9 holoenzyme

5wve, resolution 4.40Å

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