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| | ==Active human apoptosome with procaspase-9== | | ==Active human apoptosome with procaspase-9== |
| - | <StructureSection load='5juy' size='340' side='right' caption='[[5juy]], [[Resolution|resolution]] 4.10Å' scene=''> | + | <SX load='5juy' size='340' side='right' viewer='molstar' caption='[[5juy]], [[Resolution|resolution]] 4.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5juy]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JUY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5juy]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] 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=5JUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JUY FirstGlance]. <br> |
| - | </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=HEC:HEME+C'>HEC</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-9 Caspase-9], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.62 3.4.22.62] </span></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=HEC:HEME+C'>HEC</scene></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=5juy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5juy OCA], [http://pdbe.org/5juy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5juy RCSB], [http://www.ebi.ac.uk/pdbsum/5juy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5juy 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=5juy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5juy OCA], [https://pdbe.org/5juy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5juy RCSB], [https://www.ebi.ac.uk/pdbsum/5juy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5juy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/CASP9_HUMAN CASP9_HUMAN]] Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).<ref>PMID:15657060</ref> Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.<ref>PMID:15657060</ref> [[http://www.uniprot.org/uniprot/CYC_BOVIN CYC_BOVIN]] 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). | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5juy" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5juy" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Apoptotic protease-activating factor|Apoptotic protease-activating factor]] |
| | + | *[[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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Caspase-9]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Akey, C W]] | + | [[Category: Large Structures]] |
| - | [[Category: Akey, I V]] | + | [[Category: Akey CW]] |
| - | [[Category: Cheng, T C]] | + | [[Category: Akey IV]] |
| - | [[Category: Hong, C]] | + | [[Category: Cheng TC]] |
| - | [[Category: Yuan, S]] | + | [[Category: Hong C]] |
| - | [[Category: Aaa+ atpase]] | + | [[Category: Yuan S]] |
| - | [[Category: Apaf-1]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Programmed cell death]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.
A near atomic structure of the active human apoptosome.,Cheng TC, Hong C, Akey IV, Yuan S, Akey CW Elife. 2016 Oct 4;5. pii: e17755. doi: 10.7554/eLife.17755. PMID:27697150[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hu Y, Benedict MA, Ding L, Nunez G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999 Jul 1;18(13):3586-95. PMID:10393175 doi:10.1093/emboj/18.13.3586
- ↑ Ogawa T, Shiga K, Hashimoto S, Kobayashi T, Horii A, Furukawa T. APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line. Biochem Biophys Res Commun. 2003 Jun 27;306(2):537-43. PMID:12804598
- ↑ Cheng TC, Hong C, Akey IV, Yuan S, Akey CW. A near atomic structure of the active human apoptosome. Elife. 2016 Oct 4;5. pii: e17755. doi: 10.7554/eLife.17755. PMID:27697150 doi:http://dx.doi.org/10.7554/eLife.17755
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