4m9s: Difference between revisions
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==crystal structure of CED-4 bound CED-3 fragment== | |||
<StructureSection load='4m9s' size='340' side='right'caption='[[4m9s]], [[Resolution|resolution]] 3.21Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4m9s]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M9S FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.207Å</td></tr> | |||
<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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4m9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9s OCA], [https://pdbe.org/4m9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m9s RCSB], [https://www.ebi.ac.uk/pdbsum/4m9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m9s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CED4_CAEEL CED4_CAEEL] Isoform a plays a major role in programmed cell death (PCD, apoptosis). Egl-1 binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to activate the cell-killing caspase ced-3. Isoform b prevents PCD.<ref>PMID:1286611</ref> <ref>PMID:8706125</ref> <ref>PMID:9027313</ref> <ref>PMID:10688797</ref> <ref>PMID:15383288</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Programmed cell death in Caenorhabditis elegans requires activation of the caspase CED-3, which strictly depends on CED-4. CED-4 forms an octameric apoptosome, which binds the CED-3 zymogen and facilitates its autocatalytic maturation. Despite recent advances, major questions remain unanswered. Importantly, how CED-4 recognizes CED-3 and how such binding facilitates CED-3 activation remain completely unknown. Here we demonstrate that the L2' loop of CED-3 directly binds CED-4 and plays a major role in the formation of an active CED-4-CED-3 holoenzyme. The crystal structure of the CED-4 apoptosome bound to the L2' loop fragment of CED-3, determined at 3.2 A resolution, reveals specific interactions between a stretch of five hydrophobic amino acids from CED-3 and a shallow surface pocket within the hutch of the funnel-shaped CED-4 apoptosome. Structure-guided biochemical analysis confirms the functional importance of the observed CED-4-CED-3 interface. Structural analysis together with published evidence strongly suggest a working model in which two molecules of CED-3 zymogen, through specific recognition, are forced into the hutch of the CED-4 apoptosome, consequently undergoing dimerization and autocatalytic maturation. The mechanism of CED-3 activation represents a major revision of the prevailing model for initiator caspase activation. | |||
Mechanistic insights into CED-4-mediated activation of CED-3.,Huang W, Jiang T, Choi W, Qi S, Pang Y, Hu Q, Xu Y, Gong X, Jeffrey PD, Wang J, Shi Y Genes Dev. 2013 Sep 15;27(18):2039-48. doi: 10.1101/gad.224428.113. PMID:24065769<ref>PMID:24065769</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4m9s" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cell death protein 3D structures|Cell death protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Caenorhabditis elegans]] | |||
[[Category: Large Structures]] | |||
[[Category: Choi WY]] | |||
[[Category: Huang WJ]] | |||
[[Category: Jinag TY]] | |||
[[Category: Shi YG]] | |||
[[Category: Wang JW]] | |||
Latest revision as of 14:42, 8 November 2023
crystal structure of CED-4 bound CED-3 fragment
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