4m9y
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4m9y is ON HOLD Authors: Huang, WJ., Jiang, TY., Choi, WY., Wang, JW., Shi, YG. Description: crystal structure of CED-4 bound CED-3 fragment) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of CED-4 bound CED-3 fragment== | |
| + | <StructureSection load='4m9y' size='340' side='right'caption='[[4m9y]], [[Resolution|resolution]] 4.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4m9y]] is a 4 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=4M9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M9Y 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]] 4.2Å</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=4m9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9y OCA], [https://pdbe.org/4m9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m9y RCSB], [https://www.ebi.ac.uk/pdbsum/4m9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m9y 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 4m9y" 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]] | ||
Current revision
Crystal structure of CED-4 bound CED-3 fragment
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