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Contents |
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173 a.a.
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501 a.a.
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373 a.a.
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* Residue conservation analysis
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PDB id:
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Apoptosis
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Title:
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Structure of a ced-4/ced-9 complex
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Structure:
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Apoptosis regulator ced-9. Chain: a. Fragment: residues 48-251. Synonym: cell death protein 9. Engineered: yes. Mutation: yes. Ced-4. Chain: b, c. Engineered: yes
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Source:
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Caenorhabditis elegans. Organism_taxid: 6239. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expressed in: escherichia coli. Expression_system_taxid: 562
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Biol. unit:
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Trimer (from
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Resolution:
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2.60Å
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R-factor:
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0.249
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R-free:
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0.277
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Authors:
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N.Yan,Q.Liu,Q.Hao,L.Gu,Y.Shi
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Key ref:
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N.Yan
et al.
(2005).
Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans.
Nature,
437,
831-837.
PubMed id:
DOI:
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Date:
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01-Jul-05
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Release date:
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11-Oct-05
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PROCHECK
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Headers
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References
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P41958
(CED9_CAEEL) -
Apoptosis regulator ced-9 from Caenorhabditis elegans
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Seq:
Struc:
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280 a.a.
173 a.a.*
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Enzyme class:
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Chains A, B, C:
E.C.?
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DOI no:
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Nature
437:831-837
(2005)
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PubMed id:
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Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans.
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N.Yan,
J.Chai,
E.S.Lee,
L.Gu,
Q.Liu,
J.He,
J.W.Wu,
D.Kokel,
H.Li,
Q.Hao,
D.Xue,
Y.Shi.
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ABSTRACT
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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.
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Selected figure(s)
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Figure 1.
Figure 1: Overall structure of the CED-4-CED-9 complex. a, A
linear pathway of programmed cell death in C. elegans. b,
Overall structure of the CED-4-CED-9 complex. Each CED-4
molecule comprises four sequential domains--CARD domain (green),
 /
 -fold
(blue), helical domain (cyan) and winged-helix domain
(magenta)--and contains a bound ATP molecule and a magnesium
ion. c, Another view of the 2:1 CED-4-CED-9 complex. CED-4a
(green) is shown as a surface representation. The bound ATP
molecules and magnesium ions are highlighted in orange and
magenta, respectively. Figures were prepared using MOLSCRIPT
(ref. 39) and GRASP (ref. 40).
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Figure 3.
Figure 3: Structural analyses of the CED-4a-CED-4b interface and
ATP binding. a, The CED-4a-CED-4b interactions consist of a
primary (orange circle) and a secondary (magenta circle) site.
b, A stereo view of the primary interface of the CED-4 dimer.
Helices 8,
11
and 11b,
from CED-4b, stack against the CARD and /
domains
of CED-4a. c, ATP and magnesium are buried in CED-4. ATP
molecules and magnesium ions are highlighted in yellow and
magenta, respectively. d, A stereo view of ATP coordination in
CED-4. Hydrogen bonds are represented by red dashed lines. ATP
is shown in orange, with nitrogen and oxygen atoms shown in blue
and red, respectively.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2005,
437,
831-837)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.D.Galvin,
D.P.Denning,
and
H.R.Horvitz
(2011).
SPK-1, an SR protein kinase, inhibits programmed cell death in Caenorhabditis elegans.
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Proc Natl Acad Sci U S A,
108,
1998-2003.
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F.J.Tan,
J.E.Zuckerman,
R.C.Wells,
and
R.B.Hill
(2011).
The C. elegans B-cell lymphoma 2 (Bcl-2) homolog cell death abnormal 9 (CED-9) associates with and remodels LIPID membranes.
|
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Protein Sci,
20,
62-74.
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M.B.Potts,
and
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(2011).
Cell lineage and cell death: Caenorhabditis elegans and cancer research.
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Nat Rev Cancer,
11,
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S.Yuan,
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M.Topf,
L.Dorstyn,
S.Kumar,
S.J.Ludtke,
and
C.W.Akey
(2011).
Structure of the Drosophila apoptosome at 6.9 å resolution.
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Structure,
19,
128-140.
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PDB codes:
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B.B.Chandrika,
S.K.Maney,
S.U.Lekshmi,
and
S.T.Retnabhai
(2010).
Endoplasmic reticulum targeted Bcl2 confers long term cell survival through phosphorylation of heat shock protein 27.
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Int J Biochem Cell Biol,
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P.D.Mace,
and
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(2010).
Molecular cell death platforms and assemblies.
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Curr Opin Cell Biol,
22,
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S.Yuan,
X.Yu,
M.Topf,
S.J.Ludtke,
X.Wang,
and
C.W.Akey
(2010).
Structure of an apoptosome-procaspase-9 CARD complex.
|
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Structure,
18,
571-583.
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PDB codes:
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T.N.Zhang,
W.Yang,
and
N.Liu
(2010).
Effect of loop structure of bovine lactoferricin on apoptosis in Jurkat cells.
|
| |
Biometals,
23,
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|
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X.Teng,
and
J.M.Hardwick
(2010).
The apoptosome at high resolution.
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Cell,
141,
402-404.
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C.Wang,
and
R.J.Youle
(2009).
The role of mitochondria in apoptosis*.
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| |
Annu Rev Genet,
43,
95.
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|
|
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G.F.Brady,
and
C.S.Duckett
(2009).
A caspase homolog keeps CED-3 in check.
|
| |
Trends Biochem Sci,
34,
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and
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and
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Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans.
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29,
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Crystal structure of a novel archaeal AAA+ ATPase SSO1545 from Sulfolobus solfataricus.
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| |
Proteins,
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PDB code:
|
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S.J.Suhrer,
M.Wiederstein,
M.Gruber,
and
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and
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Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and apoptosis in germ cells.
|
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16,
1385-1394.
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D.Kokel,
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and
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Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9.
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| |
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|
E.Peden,
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and
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| |
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and
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|
| |
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|
|
|
|
|
|
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and
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| |
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PDB code:
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M.Proell,
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and
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and
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| |
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and
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(2008).
Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females.
|
| |
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|
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| |
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|
|
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|
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and
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(2008).
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| |
Nat Struct Mol Biol,
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|
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|
|
|
|
|
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| |
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Regulation of apoptosis by C. elegans CED-9 in the absence of the C-terminal transmembrane domain.
|
| |
Cell Death Differ,
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|
|
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| |
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and
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Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.
|
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Cell,
128,
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|
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PDB code:
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H.H.Park,
Y.C.Lo,
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and
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| |
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| |
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|
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A structural viral mimic of prosurvival Bcl-2: a pivotal role for sequestering proapoptotic Bax and Bak.
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| |
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|
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|
|
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E.F.Lee,
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| |
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U.Maurer,
and
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(2006).
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|
| |
Cell Death Differ,
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|
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|
B.A.Hay,
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(2006).
Caspase-dependent cell death in Drosophila.
|
| |
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22,
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|
B.J.DeYoung,
and
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(2006).
Plant NBS-LRR proteins in pathogen sensing and host defense.
|
| |
Nat Immunol,
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C.Adrain,
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Apoptosomes: protease activation platforms to die from.
|
| |
Trends Biochem Sci,
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(2006).
RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
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only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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