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3j2t

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{{STRUCTURE_3j2t| PDB=3j2t | SCENE= }}
 
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===An improved model of the human apoptosome===
 
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{{ABSTRACT_PUBMED_23521171}}
 
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==Function==
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==An improved model of the human apoptosome==
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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_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).
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<SX load='3j2t' size='340' side='right' viewer='molstar' caption='[[3j2t]], [[Resolution|resolution]] 9.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3j2t]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iza 3iza] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iyt 3iyt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J2T 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">Electron Microscopy, [[Resolution|Resolution]] 9.5&#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=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=3j2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j2t OCA], [https://pdbe.org/3j2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j2t RCSB], [https://www.ebi.ac.uk/pdbsum/3j2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j2t 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Apoptosome assembly is highly regulated in the intrinsic cell death pathway. To better understand this step, we created an improved model of the human apoptosome using a crystal structure of full length Apaf-1 and a single particle, electron density map at approximately 9.5 A resolution. The apoptosome model includes N-terminal domains of Apaf-1, cognate beta-propellers, and cytochrome c. A direct comparison of Apaf-1 in the apoptosome and as a monomer reveals conformational changes that occur during the first two steps of assembly. This includes an induced-fit mechanism for cytochrome c binding to regulatory beta-propellers, which is dependent on shape and charge complementarity, and a large rotation of the nucleotide binding module during nucleotide exchange. These linked conformational changes create an extended Apaf-1 monomer and drive apoptosome assembly. Moreover, the N-terminal CARD in the inactive Apaf-1 monomer is not shielded from other proteins by beta-propellers. Hence, the Apaf-1 CARD may be free to interact with a procaspase-9 CARD either before or during apoptosome assembly. Irrespective of the timing, the end product of assembly is a holo-apoptosome with an acentric CARD-CARD disk and tethered pc-9 catalytic domains. Subsequent activation of pc-9 leads to a proteolytic cascade and cell death.
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==About this Structure==
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Changes in apaf-1 conformation that drive apoptosome assembly.,Yuan S, Topf M, Reubold TF, Eschenburg S, Akey CW Biochemistry. 2013 Apr 2;52(13):2319-27. doi: 10.1021/bi301721g. Epub 2013 Mar, 22. PMID:23521171<ref>PMID:23521171</ref>
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[[3j2t]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iyt 3iyt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J2T OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:020462491</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 3j2t" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
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*[[Cytochrome C 3D structures|Cytochrome C 3D structures]]
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== References ==
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<references/>
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__TOC__
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</SX>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Akey, C W.]]
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[[Category: Large Structures]]
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[[Category: Topf, M.]]
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[[Category: Akey CW]]
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[[Category: Yuan, S.]]
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[[Category: Topf M]]
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[[Category: Apaf-1]]
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[[Category: Yuan S]]
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[[Category: Apoptosis]]
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[[Category: Apoptosis protease activating factor-1]]
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[[Category: Cytochrome c]]
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Current revision

An improved model of the human apoptosome

3j2t, resolution 9.50Å

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