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PDBsum entry 2irf
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Gene regulation/DNA
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PDB id
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2irf
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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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Crystal structure of an irf-Dna complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences.
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Authors
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Y.Fujii,
T.Shimizu,
M.Kusumoto,
Y.Kyogoku,
T.Taniguchi,
T.Hakoshima.
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Ref.
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EMBO J, 1999,
18,
5028-5041.
[DOI no: ]
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PubMed id
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Abstract
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There has been growing interest in the role of the IRF (interferon regulatory
factor) family of transcription factors in the regulation of immune responses,
cytokine signaling, and oncogenesis. These members are characterized by their
well-conserved DNA binding domains at the N-terminal regions. Here we report the
2.2 A resolution crystal structure of the DNA binding domain of one such family
member, IRF-2, bound to DNA. The structure reveals its recognition sequence,
AANNGAAA (here, recognized bases are underlined and in bold, and N indicates any
base), and its cooperative binding to a tandem repeat of the GAAA core sequence
induced by DNA structure distortions. These facts explain well the diverse
binding properties of the IRF family members, which bind to both single and
tandemly repeated sequences. Furthermore, we also identified the
'helix-hairpin-strand motif' at the C terminus of the recognition helix as a
metal binding site that is commonly found in certain classes of DNA-interactive
proteins. Our results provide new insights into the structure and function of
this family of transcription factors.
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Figure 6.
Figure 6 Model for PU.1 and IRF-4 bound to DNA. A side view of
surface representation showing the model for DNA binding domains
of PU.1 (green) and IRF-4 (purple) bound to DNA (light green)
containing the GGAANNGAAA motif in the  B
site of the enhancer of the immunoglobulin light chain gene.
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Figure 7.
Figure 7 Possible synergistic bindings at enhancer elements. (A)
A side view of the surface representation of the IFN-  enhancer
with the DNA binding domains of the transcription factors; IRFs
(purple and wine red) bound to the PRD III and I sites, ATF-2
-c-Jun (blue and green) bound to the PRD IV, and NF-  B,
p65 (light green) -p50 (light blue) heterodimer bound to the PRD
I sites. The DNA sequence and the binding sites are indicated at
the top. Minor grooves of the HMG I(Y) binding sites are
indicated with labels. The N and C termini are indicated to show
the locations of their activation domains that link to the N
termini of ATF-2 -Jun and the C termini of IRF and p65. (B) A
side view of the surface representation showing the IRF-2 DNA
binding domains (purple and wine red) bound to the TATA-box
region of the VCAM-1 gene, together with bound TBP (light blue)
and the TFIIB core (green). An IRF-2 DNA binding domain (purple)
bound to the upstream GAAA core sequence contacts with the
N-terminal domain of the TFIIB core.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
5028-5041)
copyright 1999.
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