3jbt: Difference between revisions
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''' | ==Atomic structure of the Apaf-1 apoptosome== | ||
<StructureSection load='3jbt' size='340' side='right' caption='[[3jbt]], [[Resolution|resolution]] 3.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3jbt]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBT 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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=3jbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbt OCA], [http://pdbe.org/3jbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbt RCSB], [http://www.ebi.ac.uk/pdbsum/3jbt PDBsum]</span></td></tr> | |||
</table> | |||
== 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/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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 A resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. | |||
Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.,Zhou M, Li Y, Hu Q, Bai XC, Huang W, Yan C, Scheres SH, Shi Y Genes Dev. 2015 Nov 15;29(22):2349-61. doi: 10.1101/gad.272278.115. Epub 2015 Nov, 5. PMID:26543158<ref>PMID:26543158</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3jbt" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Equus caballus]] | |||
[[Category: Bai, X]] | |||
[[Category: Hu, Q]] | |||
[[Category: Huang, W]] | [[Category: Huang, W]] | ||
[[Category: Li, Y]] | [[Category: Li, Y]] | ||
[[Category: Scheres, S H.W]] | |||
[[Category: Shi, Y]] | |||
[[Category: Yan, C]] | [[Category: Yan, C]] | ||
[[Category: Zhou, M]] | [[Category: Zhou, M]] | ||
[[Category: | [[Category: Apaf-1]] | ||
[[Category: Apoptosis]] | |||
[[Category: Apoptosome]] | |||
[[Category: Cryo-em structure]] | |||
