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1z6t

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(New page: 200px<br /> <applet load="1z6t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z6t, resolution 2.21&Aring;" /> '''Structure of the ap...)
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[[Image:1z6t.gif|left|200px]]<br />
 
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<applet load="1z6t" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1z6t, resolution 2.21&Aring;" />
 
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'''Structure of the apoptotic protease-activating factor 1 bound to ADP'''<br />
 
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==Overview==
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==Structure of the apoptotic protease-activating factor 1 bound to ADP==
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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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<StructureSection load='1z6t' size='340' side='right'caption='[[1z6t]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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== Structural highlights ==
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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='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='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>
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</table>
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== Function ==
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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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<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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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=1z6t ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1Z6T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ADP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Z6T OCA].
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*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
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== References ==
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==Reference==
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<references/>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15829969 15829969]
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__TOC__
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</StructureSection>
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[[Category: Apoptosomes]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Chao, Y.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Li, W.]]
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[[Category: Chao Y]]
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[[Category: Riedl, S.J.]]
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[[Category: Li W]]
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[[Category: Schwarzenbacher, R.]]
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[[Category: Riedl SJ]]
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[[Category: Shi, Y.]]
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[[Category: Schwarzenbacher R]]
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[[Category: ADP]]
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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: card]]
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[[Category: caspase activation]]
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[[Category: nucleotide binding]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:30:01 2007''
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Current revision

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

PDB ID 1z6t

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