8jns

From Proteopedia

(Difference between revisions)

Current revision

cryo-EM structure of a CED-4 hexamer

Structural highlights

8jns is a 9 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.2Å
Ligands:	,
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

In Caenorhabditis elegans (C. elegans), onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to cleave a wide range of substrates, leading to irreversible cell death. Despite decades of investigations, the underlying mechanism of CED-4-facilitated CED-3 activation remains elusive. Here, we report cryo-EM structures of the CED-4 apoptosome and three distinct CED-4/CED-3 complexes that mimic different activation stages for CED-3. In addition to the previously reported octamer in crystal structures, CED-4, alone or in complex with CED-3, exists in multiple oligomeric states. Supported by biochemical analyses, we show that the conserved CARD-CARD interaction promotes CED-3 activation, and initiation of programmed cell death is regulated by the dynamic organization of the CED-4 apoptosome.

Structural insights into CED-3 activation.,Li Y, Tian L, Zhang Y, Shi Y Life Sci Alliance. 2023 Jul 4;6(9):e202302056. doi: 10.26508/lsa.202302056. Print , 2023 Sep. PMID:37402593^[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
↑ Li Y, Tian L, Zhang Y, Shi Y. Structural insights into CED-3 activation. Life Sci Alliance. 2023 Jul 4;6(9):e202302056. PMID:37402593 doi:10.26508/lsa.202302056

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8jns"

Categories: Caenorhabditis elegans | Large Structures | Li Y | Shi Y

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jns is ON HOLD
+==cryo-EM structure of a CED-4 hexamer==
+<StructureSection load='8jns' size='340' side='right'caption='[[8jns]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jns]] is a 9 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=8JNS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JNS FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</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></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=8jns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jns OCA], [https://pdbe.org/8jns PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jns RCSB], [https://www.ebi.ac.uk/pdbsum/8jns PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jns 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 ==
+In Caenorhabditis elegans (C. elegans), onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to cleave a wide range of substrates, leading to irreversible cell death. Despite decades of investigations, the underlying mechanism of CED-4-facilitated CED-3 activation remains elusive. Here, we report cryo-EM structures of the CED-4 apoptosome and three distinct CED-4/CED-3 complexes that mimic different activation stages for CED-3. In addition to the previously reported octamer in crystal structures, CED-4, alone or in complex with CED-3, exists in multiple oligomeric states. Supported by biochemical analyses, we show that the conserved CARD-CARD interaction promotes CED-3 activation, and initiation of programmed cell death is regulated by the dynamic organization of the CED-4 apoptosome.
-Authors: Yini, L., Yigong, S.
+Structural insights into CED-3 activation.,Li Y, Tian L, Zhang Y, Shi Y Life Sci Alliance. 2023 Jul 4;6(9):e202302056. doi: 10.26508/lsa.202302056. Print , 2023 Sep. PMID:37402593<ref>PMID:37402593</ref>
-Description: cryo-EM structure of a CED-4 hexamer
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Yigong, S]]
+<div class="pdbe-citations 8jns" style="background-color:#fffaf0;"></div>
-[[Category: Yini, L]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Caenorhabditis elegans]]
+[[Category: Large Structures]]
+[[Category: Li Y]]
+[[Category: Shi Y]]

8jns

From Proteopedia

Current revision

cryo-EM structure of a CED-4 hexamer

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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