1z6t

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==Structure of the apoptotic protease-activating factor 1 bound to ADP==
==Structure of the apoptotic protease-activating factor 1 bound to ADP==
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<StructureSection load='1z6t' size='340' side='right' caption='[[1z6t]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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<StructureSection load='1z6t' size='340' side='right'caption='[[1z6t]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1z6t]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The September 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Apoptosomes'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_9 10.2210/rcsb_pdb/mom_2014_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z6T FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1z6t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The September 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Apoptosomes'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_9 10.2210/rcsb_pdb/mom_2014_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z6T 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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21&#8491;</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=1z6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z6t OCA], [http://pdbe.org/1z6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z6t RCSB], [http://www.ebi.ac.uk/pdbsum/1z6t PDBsum]</span></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z6t OCA], [https://pdbe.org/1z6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z6t RCSB], [https://www.ebi.ac.uk/pdbsum/1z6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z6t ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>
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[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>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/1z6t_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/1z6t_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1z6t ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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Apoptosis is executed by caspases, which undergo proteolytic activation in response to cell death stimuli. The apoptotic protease-activating factor 1 (Apaf-1) controls caspase activation downstream of mitochondria. During apoptosis, Apaf-1 binds to cytochrome c and in the presence of ATP/dATP forms an apoptosome, leading to the recruitment and activation of the initiator caspase, caspase-9 (ref. 2). The mechanisms underlying Apaf-1 function are largely unknown. Here we report the 2.2-A crystal structure of an ADP-bound, WD40-deleted Apaf-1, which reveals the molecular mechanism by which Apaf-1 exists in an inactive state before ATP binding. The amino-terminal caspase recruitment domain packs against a three-layered alpha/beta fold, a short helical motif and a winged-helix domain, resulting in the burial of the caspase-9-binding interface. The deeply buried ADP molecule serves as an organizing centre to strengthen interactions between these four adjoining domains, thus locking Apaf-1 in an inactive conformation. Apaf-1 binds to and hydrolyses ATP/dATP and their analogues. The binding and hydrolysis of nucleotides seem to drive conformational changes that are essential for the formation of the apoptosome and the activation of caspase-9.
 
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Structure of the apoptotic protease-activating factor 1 bound to ADP.,Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y Nature. 2005 Apr 14;434(7035):926-33. PMID:15829969<ref>PMID:15829969</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
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<div class="pdbe-citations 1z6t" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Apoptosomes]]
[[Category: Apoptosomes]]
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Chao, Y]]
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[[Category: Chao Y]]
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[[Category: Li, W]]
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[[Category: Li W]]
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[[Category: Riedl, S J]]
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[[Category: Riedl SJ]]
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[[Category: Schwarzenbacher, R]]
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[[Category: Schwarzenbacher R]]
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[[Category: Shi, Y]]
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[[Category: Shi Y]]
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[[Category: Adp]]
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[[Category: Apaf-1]]
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[[Category: Apoptosis]]
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[[Category: Card]]
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[[Category: Caspase activation]]
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[[Category: Nucleotide binding]]
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Current revision

Structure of the apoptotic protease-activating factor 1 bound to ADP

PDB ID 1z6t

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