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PDBsum entry 2bbz
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Viral protein
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PDB id
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2bbz
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Contents |
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* Residue conservation analysis
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PDB id:
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Viral protein
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Title:
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Crystal structure of mc159 reveals molecular mechanism of disc assembly and vflip inhibition
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Structure:
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Viral casp8 and fadd-like apoptosis regulator. Chain: a, b, c, d. Synonym: v-cflar, viral flice-inhibitory protein, v-flip. Engineered: yes
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Source:
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Molluscum contagiosum virus subtype 1. Organism_taxid: 10280. Strain: subtype 1. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Monomer (from
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Resolution:
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3.80Å
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R-factor:
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0.325
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R-free:
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0.372
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Authors:
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J.K.Yang,L.Wang,L.Zheng,F.Wan,M.Ahmed,M.J.Lenardo,H.Wu
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Key ref:
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J.K.Yang
et al.
(2005).
Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition.
Mol Cell,
20,
939-949.
PubMed id:
DOI:
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Date:
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18-Oct-05
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Release date:
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14-Feb-06
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PROCHECK
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Headers
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References
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Q98325
(CFLA_MCV1) -
Viral CASP8 and FADD-like apoptosis regulator from Molluscum contagiosum virus subtype 1
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Seq:
Struc:
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241 a.a.
190 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Mol Cell
20:939-949
(2005)
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PubMed id:
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Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition.
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J.K.Yang,
L.Wang,
L.Zheng,
F.Wan,
M.Ahmed,
M.J.Lenardo,
H.Wu.
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ABSTRACT
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The death-inducing signaling complex (DISC) comprising Fas, Fas-associated death
domain (FADD), and caspase-8/10 is assembled via homotypic associations between
death domains (DDs) of Fas and FADD and between death effector domains (DEDs) of
FADD and caspase-8/10. Caspase-8/10 and FLICE/caspase-8 inhibitory proteins
(FLIPs) that inhibit caspase activation at the DISC level contain tandem DEDs.
Here, we report the crystal structure of a viral FLIP, MC159, at 1.2 Angstroms
resolution. It reveals a noncanonical fold of DED1, a dumbbell-shaped structure
with rigidly associated DEDs and a different mode of interaction in the DD
superfamily. Whereas the conserved hydrophobic patch of DED1 interacts with
DED2, the corresponding region of DED2 mediates caspase-8 recruitment and
contributes to DISC assembly. In contrast, MC159 cooperatively assembles with
Fas and FADD via an extensive surface that encompasses the conserved charge
triad. This interaction apparently competes with FADD self-association and
disrupts higher-order oligomerization required for caspase activation in the
DISC.
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Selected figure(s)
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Figure 2.
Figure 2. Crystal Structure of MC159
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Figure 3.
Figure 3. Mode of Interaction between DED1 and DED2
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
20,
939-949)
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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A.Rajput,
A.Kovalenko,
K.Bogdanov,
S.H.Yang,
T.B.Kang,
J.C.Kim,
J.Du,
and
D.Wallach
(2011).
RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein.
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Immunity,
34,
340-351.
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M.S.Ola,
M.Nawaz,
and
H.Ahsan
(2011).
Role of Bcl-2 family proteins and caspases in the regulation of apoptosis.
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Mol Cell Biochem,
351,
41-58.
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B.Farina,
L.Pirone,
L.Russo,
F.Viparelli,
N.Doti,
C.Pedone,
E.M.Pedone,
and
R.Fattorusso
(2010).
NMR backbone dynamics studies of human PED/PEA-15 outline protein functional sites.
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FEBS J,
277,
4229-4240.
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L.Wang,
J.K.Yang,
V.Kabaleeswaran,
A.J.Rice,
A.C.Cruz,
A.Y.Park,
Q.Yin,
E.Damko,
S.B.Jang,
S.Raunser,
C.V.Robinson,
R.M.Siegel,
T.Walz,
and
H.Wu
(2010).
The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations.
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Nat Struct Mol Biol,
17,
1324-1329.
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PDB code:
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S.Challa,
and
F.K.Chan
(2010).
Going up in flames: necrotic cell injury and inflammatory diseases.
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Cell Mol Life Sci,
67,
3241-3253.
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T.H.Jang,
C.Zheng,
H.Wu,
J.H.Jeon,
and
H.H.Park
(2010).
In vitro reconstitution of the interactions in the PIDDosome.
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Apoptosis,
15,
1444-1452.
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E.de Alba
(2009).
Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC).
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J Biol Chem,
284,
32932-32941.
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PDB code:
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J.S.Lee,
Q.Li,
J.Y.Lee,
S.H.Lee,
J.H.Jeong,
H.R.Lee,
H.Chang,
F.C.Zhou,
S.J.Gao,
C.Liang,
and
J.U.Jung
(2009).
FLIP-mediated autophagy regulation in cell death control.
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Nat Cell Biol,
11,
1355-1362.
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Q.Wang,
M.Liu,
X.Li,
L.Chen,
and
H.Tang
(2009).
Kazrin F is involved in apoptosis and interacts with BAX and ARC.
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Acta Biochim Biophys Sin (Shanghai),
41,
763-772.
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Q.Yin,
S.C.Lin,
B.Lamothe,
M.Lu,
Y.C.Lo,
G.Hura,
L.Zheng,
R.L.Rich,
A.D.Campos,
D.G.Myszka,
M.J.Lenardo,
B.G.Darnay,
and
H.Wu
(2009).
E2 interaction and dimerization in the crystal structure of TRAF6.
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Nat Struct Mol Biol,
16,
658-666.
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PDB codes:
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C.Bagnéris,
A.V.Ageichik,
N.Cronin,
B.Wallace,
M.Collins,
C.Boshoff,
G.Waksman,
and
T.Barrett
(2008).
Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome.
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Mol Cell,
30,
620-631.
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PDB code:
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J.G.Albeck,
J.M.Burke,
S.L.Spencer,
D.A.Lauffenburger,
and
P.K.Sorger
(2008).
Modeling a snap-action, variable-delay switch controlling extrinsic cell death.
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PLoS Biol,
6,
2831-2852.
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J.K.Yang
(2008).
FLIP as an anti-cancer therapeutic target.
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Yonsei Med J,
49,
19-27.
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J.W.Yu,
and
Y.Shi
(2008).
FLIP and the death effector domain family.
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Oncogene,
27,
6216-6227.
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N.Ueffing,
E.Keil,
C.Freund,
R.Kühne,
K.Schulze-Osthoff,
and
I.Schmitz
(2008).
Mutational analyses of c-FLIPR, the only murine short FLIP isoform, reveal requirements for DISC recruitment.
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Cell Death Differ,
15,
773-782.
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S.M.Best
(2008).
Viral subversion of apoptotic enzymes: escape from death row.
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Annu Rev Microbiol,
62,
171-192.
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T.W.Day,
S.Huang,
and
A.R.Safa
(2008).
c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells.
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Biochem Pharmacol,
76,
1694-1704.
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H.H.Park,
E.Logette,
S.Raunser,
S.Cuenin,
T.Walz,
J.Tschopp,
and
H.Wu
(2007).
Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.
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Cell,
128,
533-546.
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PDB code:
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H.H.Park,
Y.C.Lo,
S.C.Lin,
L.Wang,
J.K.Yang,
and
H.Wu
(2007).
The death domain superfamily in intracellular signaling of apoptosis and inflammation.
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Annu Rev Immunol,
25,
561-586.
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H.Matta,
L.Mazzacurati,
S.Schamus,
T.Yang,
Q.Sun,
and
P.M.Chaudhary
(2007).
Kaposi's sarcoma-associated herpesvirus (KSHV) oncoprotein K13 bypasses TRAFs and directly interacts with the IkappaB kinase complex to selectively activate NF-kappaB without JNK activation.
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J Biol Chem,
282,
24858-24865.
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L.Sanchez-Pulido,
A.Valencia,
and
A.M.Rojas
(2007).
Are promyelocytic leukaemia protein nuclear bodies a scaffold for caspase-2 programmed cell death?
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Trends Biochem Sci,
32,
400-406.
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Q.Bao,
and
Y.Shi
(2007).
Apoptosome: a platform for the activation of initiator caspases.
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Cell Death Differ,
14,
56-65.
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S.J.Riedl,
and
G.S.Salvesen
(2007).
The apoptosome: signalling platform of cell death.
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Nat Rev Mol Cell Biol,
8,
405-413.
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A.Natarajan,
R.Ghose,
and
J.M.Hill
(2006).
Structure and dynamics of ASC2, a pyrin domain-only protein that regulates inflammatory signaling.
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J Biol Chem,
281,
31863-31875.
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PDB code:
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C.Sandu,
G.Morisawa,
I.Wegorzewska,
T.Huang,
A.F.Arechiga,
J.M.Hill,
T.Kim,
C.M.Walsh,
and
M.H.Werner
(2006).
FADD self-association is required for stable interaction with an activated death receptor.
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Cell Death Differ,
13,
2052-2061.
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J.R.Muppidi,
A.A.Lobito,
M.Ramaswamy,
J.K.Yang,
L.Wang,
H.Wu,
and
R.M.Siegel
(2006).
Homotypic FADD interactions through a conserved RXDLL motif are required for death receptor-induced apoptosis.
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Cell Death Differ,
13,
1641-1650.
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N.Festjens,
S.Cornelis,
M.Lamkanfi,
and
P.Vandenabeele
(2006).
Caspase-containing complexes in the regulation of cell death and inflammation.
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Biol Chem,
387,
1005-1016.
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P.E.Carrington,
C.Sandu,
Y.Wei,
J.M.Hill,
G.Morisawa,
T.Huang,
E.Gavathiotis,
Y.Wei,
and
M.H.Werner
(2006).
The structure of FADD and its mode of interaction with procaspase-8.
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Mol Cell,
22,
599-610.
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PDB code:
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Y.B.Chen,
S.Y.Seo,
D.G.Kirsch,
T.T.Sheu,
W.C.Cheng,
and
J.M.Hardwick
(2006).
Alternate functions of viral regulators of cell death.
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Cell Death Differ,
13,
1318-1324.
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Y.Shi
(2006).
Mechanical aspects of apoptosome assembly.
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Curr Opin Cell Biol,
18,
677-684.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
