4m9s: Difference between revisions

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{{STRUCTURE_4m9s| PDB=4m9s |  SCENE= }}
==crystal structure of CED-4 bound CED-3 fragment==
===crystal structure of CED-4 bound CED-3 fragment===
<StructureSection load='4m9s' size='340' side='right' caption='[[4m9s]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
{{ABSTRACT_PUBMED_24065769}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4m9s]] is a 8 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M9S FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lqq|3lqq]], [[4m9x|4m9x]], [[4m9y|4m9y]], [[4m9z|4m9z]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ced-4, C35D10.9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 Caenorhabditis elegans])</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=4m9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m9s RCSB], [http://www.ebi.ac.uk/pdbsum/4m9s PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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.


==Function==
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>
[[http://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>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4m9s]] is a 8 chain structure with sequence from [http://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].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:024065769</ref><references group="xtra"/><references/>
*[[Cell death protein|Cell death protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Caenorhabditis elegans]]
[[Category: Choi, W Y.]]
[[Category: Choi, W Y]]
[[Category: Huang, W J.]]
[[Category: Huang, W J]]
[[Category: Jinag, T Y.]]
[[Category: Jinag, T Y]]
[[Category: Shi, Y G.]]
[[Category: Shi, Y G]]
[[Category: Wang, J W.]]
[[Category: Wang, J W]]
[[Category: Apoptosis]]
[[Category: Apoptosis]]
[[Category: Apoptosome]]
[[Category: Apoptosome]]
[[Category: Ced-3]]
[[Category: Ced-3]]
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