 |
PDBsum entry 1j2f
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
DNA binding protein
|
PDB id
|
|
|
|
1j2f
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
X-Ray crystal structure of irf-3 and its functional implications.
|
|
|
Authors
|
|
K.Takahasi,
N.N.Suzuki,
M.Horiuchi,
M.Mori,
W.Suhara,
Y.Okabe,
Y.Fukuhara,
H.Terasawa,
S.Akira,
T.Fujita,
F.Inagaki.
|
|
|
Ref.
|
|
Nat Struct Biol, 2003,
10,
922-927.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Transcription factor IRF-3 is post-translationally activated by Toll-like
receptor (TLR) signaling and has critical roles in the regulation of innate
immunity. Here we present the X-ray crystal structure of the C-terminal
regulatory domain of IRF-3(175-427) (IRF-3 175C) at a resolution of 2.3 A. IRF-3
175C is structurally similar to the Mad homology domain 2 of the Smad family.
Structural and functional analyses reveal phosphorylation-induced IRF-3
dimerization, which generates an extensive acidic pocket responsible for binding
with p300/CBP. Although TLR and Smad signaling are evolutionarily independent,
our results suggest that IRF-3 originates from Smad and acquires its function
downstream of TLR.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Overall structure of IRF-3 and its structural
similarity to Smad2. (a) A stereo view of the C  trace
of the IRF-3 175C homodimer in the asymmetric unit. Subunits A
and B are blue and red, respectively. Dotted circles represent
the LHR-pocket. This figure was prepared with MolScript33. (b,c)
Ribbon diagram representations of the IRF-3 175C monomer. SRR is
cyan, and a disordered loop is indicated by a dotted line. b and
c are related by a 90° rotation along the horizontal axis. (d)
Comparison of the structures of IRF-3 175C (left) and Smad2
(right). The structurally similar region between IRF-3 175C and
Smad2 is in cyan and others are in yellow. All figures except
Figures 2a, 3b and 4 were prepared with MolScript and
Raster3D^34.
|
|
Figure 5.
Figure 5. Acidic surface of IRF-3. (a) The electrostatic
surface potential representation of the IRF-3 homodimer. The
surface corresponds to the opposite surface shown in Figure 2a.
Figure 5a was prepared with GRASP36 and Raster3D^34. (b) Dimer
formation of the E/A mutant. Expression vectors for p50-tagged
wild type and the E/A mutant of IRF-3 were transiently expressed
in L929 cells. After mock treatment (-) or infection with NDV
for 12 h (+), the extracts were prepared and subjected to native
PAGE using anti-p50-tag as a probe. (c) Critical role of
glutamate residues in the association of p50-tagged IRF-3 with
p300/CBP. The extracts in Figure 5c were immunoprecipitated with
anti-NES, and resolved by SDS-PAGE followed by immunoblotting
with anti-p300/CBP (top) or anti-p50-tag (bottom).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
922-927)
copyright 2003.
|
|
|
|
|
|
|
