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PDBsum entry 1d0a
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structural basis for the recognition of diverse receptor sequences by traf2.
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Authors
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H.Ye,
Y.C.Park,
M.Kreishman,
E.Kieff,
H.Wu.
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Ref.
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Mol Cell, 1999,
4,
321-330.
[DOI no: ]
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PubMed id
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Abstract
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Many members of the tumor necrosis factor receptor (TNFR) superfamily initiate
intracellular signaling by recruiting TNFR-associated factors (TRAFs) through
their cytoplasmic tails. TRAFs apparently recognize highly diverse receptor
sequences. Crystal structures of the TRAF domain of human TRAF2 in complex with
peptides from the TNFR family members CD40, CD30, Ox40, 4-1BB, and the EBV
oncoprotein LMP1 revealed a conserved binding mode. A major TRAF2-binding
consensus sequence, (P/S/A/T)x(Q/E)E, and a minor consensus motif, PxQxxD, can
be defined from the structural analysis, which encompass all known TRAF2-binding
sequences. The structural information provides a template for the further
dissection of receptor binding specificity of TRAF2 and for the understanding of
the complexity of TRAF-mediated signal transduction.
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Figure 3.
Figure 3. Detailed Interactions for the Major Consensus
Motif (P/S/A/T)x(Q/E)EShown is the stereo diagram of the
interaction between the TRAF domain and the CD40 peptide, with
the molecular 3-fold axis vertical. The TRAF domain is
represented by purple worm-and-stick models, with carbon atoms
in gray. The peptide is shown as a stick model, with carbon
atoms in yellow. The side chain at the P[−1] position and the
entire chain after the amide of the P[2] position are omitted
for clarity. The conformations of the two CD40 peptides with
different lengths (Table 1) are essentially identical. Atoms
within hydrogen-bonding distances are connected with black
dotted lines. The β strands in the path of the peptide and
selected residues in the TRAF domain are labeled. Note the
interactions at the P[−2], P[0], and P[1] positions of the
peptide.
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Figure 5.
Figure 5. A Model for the Activated TRAF–Receptor
ComplexThe atomic coordinates for the complex between a TNF-like
ligand and a TNFR were taken from PDB entry 1tnr and are shown
as thin worms (green, light blue, and darker blue) for the
ligand and thick worms (pink, orange, and blue) for the
receptor. The TRAF domain structure from the CD40 complex is
shown as ribbon traces, with the β strands in green, cyan, and
dark blue for each of the protomers of the trimer. The receptor
peptides (pink, orange, and blue) are shown as the CD40 peptide
with an extended amino terminus from the CD30 peptide. Dotted
lines are used to connect the extracellular and the
intracellular portions of the receptor. The amino-terminal RING
and zinc finger domains of the TRAF trimer are shown as green
ovals. Cell membrane is represented in yellow.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(1999,
4,
321-330)
copyright 1999.
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Secondary reference #1
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Title
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Structural basis for self-Association and receptor recognition of human traf2.
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Authors
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Y.C.Park,
V.Burkitt,
A.R.Villa,
L.Tong,
H.Wu.
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Ref.
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Nature, 1999,
398,
533-538.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1: Structure of the TRAF domain alone and in complex with
the TNF-R2 peptide. a, Stereo ribbon diagram of the TRAF
domain of human TRAF2 in the peptide-free structure. The  -strands,
 -helices
and loops are shown in cyan, yellow and purple, respectively.
The loop between 7
and 8
is highly flexible andexhibits a different conformation in the
peptide-bound structure b, Ribbon drawing of the trimeric TRAF
domain in complex with TNF-R2 peptide, looking down the
three-fold axis. The -strands
in each protomer are shown in cyan, green and dark blue. The
peptide is shown as a stick model for the protomer incyan.
Residues of the TRAF-C domain in the trimer interface (between
the protomers shown in cyan and dark blue) are also shown as
stick models. The TRAF-C domain of the structure obeys proper
three-fold symmetry, whereas the coiled-coil domain shows
significant deviations. c, As for b, except that the three-fold
axis is now vertical.
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Figure 3.
Figure 3: Detailed interaction between TRAF2 and the TNF-R2
peptide. a,Simulated annealing omit difference map for the
TNF-R2 peptide calculated with reflections between 20.0 and 2.3
Å resolution and contoured at 2.0  .
The peptide model is superimposed. b, Molecular surface of a
TRAF2 promoter, showing the bound TNF-R2 peptide as a stick
model; the three-fold axis is in the vertical orientation.
Surface colour coding is according to electrostatic surface
potential, scaled from -30 to +30 kTe^-1, with blue for positive
and red for negative. Selected residues in the receptor peptide
and the underlying secondary-structural elements of TRAF2 at the
binding site are labelled. c, Stereo view of the detailed
interaction between the TNF-R2 peptide (carbon atoms shown in
yellow) and the TRAF2 protomer (carbon atoms shown in grey). The
main chain of the TRAF2 structure is shown in cyan as backbone
worms. Selected residues in the peptide (primed numbers in
green) and the protein (in grey) are labelled. Hydrogen bonds
and a salt bridge are shown as black dotted lines.
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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