This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4m9x

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 10:33, 4 August 2016

Crystal structure of CED-4 bound CED-3 fragment

Structural highlights

4m9x is a 4 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4m9s, 4m9y, 4m9z
Gene:	ced-4, C35D10.9 (CAEEL)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yuan J, Horvitz HR. The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development. 1992 Oct;116(2):309-20. PMID:1286611
↑ Shaham S, Horvitz HR. An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor. Cell. 1996 Jul 26;86(2):201-8. PMID:8706125
↑ Wu D, Wallen HD, Nunez G. Interaction and regulation of subcellular localization of CED-4 by CED-9. Science. 1997 Feb 21;275(5303):1126-9. PMID:9027313
↑ Chen F, Hersh BM, Conradt B, Zhou Z, Riemer D, Gruenbaum Y, Horvitz HR. Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science. 2000 Feb 25;287(5457):1485-9. PMID:10688797
↑ Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 Sep 24;15(6):999-1006. PMID:15383288 doi:10.1016/j.molcel.2004.08.022
↑ Huang W, Jiang T, Choi W, Qi S, Pang Y, Hu Q, Xu Y, Gong X, Jeffrey PD, Wang J, Shi Y. Mechanistic insights into CED-4-mediated activation of CED-3. Genes Dev. 2013 Sep 15;27(18):2039-48. doi: 10.1101/gad.224428.113. PMID:24065769 doi:http://dx.doi.org/10.1101/gad.224428.113

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4m9x"

@@ Line 1: / Line 1: @@
 ==Crystal structure of CED-4 bound CED-3 fragment==
 <StructureSection load='4m9x' size='340' side='right' caption='[[4m9x]], [[Resolution|resolution]] 3.34&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4m9x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopus_itombwensis Xenopus itombwensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M9X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4m9x]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M9X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M9X 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m9s|4m9s]], [[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=542840 Xenopus itombwensis])</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 CAEEL])</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=4m9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m9x RCSB], [http://www.ebi.ac.uk/pdbsum/4m9x PDBsum]</span></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=4m9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m9x OCA], [http://pdbe.org/4m9x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m9x RCSB], [http://www.ebi.ac.uk/pdbsum/4m9x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m9x ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4m9x" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Xenopus itombwensis]]
+[[Category: Caeel]]
 [[Category: Choi, W Y]]
 [[Category: Huang, W J]]

4m9x

From Proteopedia

Revision as of 10:33, 4 August 2016

Crystal structure of CED-4 bound CED-3 fragment

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox