2a5y: Difference between revisions

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New page: left|200px<br /><applet load="2a5y" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a5y, resolution 2.6Å" /> '''Structure of a CED-4/...
 
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[[Image:2a5y.gif|left|200px]]<br /><applet load="2a5y" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2a5y, resolution 2.6&Aring;" />
'''Structure of a CED-4/CED-9 complex'''<br />


==Overview==
==Structure of a CED-4/CED-9 complex==
Interplay among four genes--egl-1, ced-9, ced-4 and ced-3--controls the, onset of programmed cell death in the nematode Caenorhabditis elegans., Activation of the cell-killing protease CED-3 requires CED-4. However, CED-4 is constitutively inhibited by CED-9 until its release by EGL-1., Here we report the crystal structure of the CED-4-CED-9 complex at 2.6 A, resolution, and a complete reconstitution of the CED-3 activation pathway, using homogeneous proteins of CED-4, CED-9 and EGL-1. One molecule of, CED-9 binds to an asymmetric dimer of CED-4, but specifically recognizes, only one of the two CED-4 molecules. This specific interaction prevents, CED-4 from activating CED-3. EGL-1 binding induces pronounced, conformational changes in CED-9 that result in the dissociation of the, CED-4 dimer from CED-9. The released CED-4 dimer further dimerizes to form, a tetramer, which facilitates the autoactivation of CED-3. Together, our, studies provide important insights into the regulation of cell death, activation in C. elegans.
<StructureSection load='2a5y' size='340' side='right'caption='[[2a5y]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2a5y]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. The September 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Apoptosomes''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_9 10.2210/rcsb_pdb/mom_2014_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A5Y 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]] 2.6&#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=2a5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a5y OCA], [https://pdbe.org/2a5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a5y RCSB], [https://www.ebi.ac.uk/pdbsum/2a5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a5y ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CED9_CAEEL CED9_CAEEL] 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.<ref>PMID:7907274</ref> <ref>PMID:9024666</ref> <ref>PMID:9027313</ref> <ref>PMID:9604928</ref> <ref>PMID:10688797</ref> <ref>PMID:15383288</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a5/2a5y_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2a5y ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2A5Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] with MG and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A5Y OCA].
*[[Cell death protein 3D structures|Cell death protein 3D structures]]
 
== References ==
==Reference==
<references/>
Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans., Yan N, Chai J, Lee ES, Gu L, Liu Q, He J, Wu JW, Kokel D, Li H, Hao Q, Xue D, Shi Y, Nature. 2005 Oct 6;437(7060):831-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16208361 16208361]
__TOC__
</StructureSection>
[[Category: Apoptosomes]]
[[Category: Caenorhabditis elegans]]
[[Category: Caenorhabditis elegans]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Gu, L.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Hao, Q.]]
[[Category: Gu L]]
[[Category: Liu, Q.]]
[[Category: Hao Q]]
[[Category: Shi, Y.]]
[[Category: Liu Q]]
[[Category: Yan, N.]]
[[Category: Shi Y]]
[[Category: ATP]]
[[Category: Yan N]]
[[Category: MG]]
[[Category: apoptosis]]
[[Category: ced-3 activation]]
[[Category: ced-4]]
[[Category: ced-9]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:56:08 2007''

Latest revision as of 12:11, 14 February 2024

Structure of a CED-4/CED-9 complexStructure of a CED-4/CED-9 complex

Structural highlights

2a5y is a 3 chain structure with sequence from Caenorhabditis elegans. The September 2014 RCSB PDB Molecule of the Month feature on Apoptosomes by David Goodsell is 10.2210/rcsb_pdb/mom_2014_9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CED9_CAEEL 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.[1] [2] [3] [4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994 Feb 25;76(4):665-76. PMID:7907274
  2. ↑ Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO. Interaction between the C. elegans cell-death regulators CED-9 and CED-4. Nature. 1997 Feb 13;385(6617):653-6. PMID:9024666 doi:http://dx.doi.org/10.1038/385653a0
  3. ↑ 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
  4. ↑ Conradt B, Horvitz HR. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell. 1998 May 15;93(4):519-29. PMID:9604928
  5. ↑ 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
  6. ↑ 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

2a5y, resolution 2.60Å

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