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PDBsum entry 2a5y
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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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References listed in PDB file
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Key reference
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Title
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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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Authors
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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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Ref.
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Nature, 2005,
437,
831-837.
[DOI no: ]
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PubMed id
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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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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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