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PDBsum entry 1j2f
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DNA binding protein PDB id
1j2f

 

 

 

 

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Contents
Protein chain
226 a.a. *
Waters ×160
* Residue conservation analysis
PDB id:
1j2f
Name: DNA binding protein
Title: X-ray crystal structure of irf-3 and its functional implications
Structure: Interferon regulatory factor 3. Chain: a, b. Fragment: residues 170-427. Synonym: irf-3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.217     R-free:   0.242
Authors: K.Takahasi,N.Noda,M.Horiuchi,M.Mori,Y.Okabe,Y.Fukuhara,H.Terasawa, T.Fujita,F.Inagaki
Key ref:
K.Takahasi et al. (2003). X-ray crystal structure of IRF-3 and its functional implications. Nat Struct Biol, 10, 922-927. PubMed id: 14555995 DOI: 10.1038/nsb1001
Date:
04-Jan-03     Release date:   25-Nov-03    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q14653  (IRF3_HUMAN) -  Interferon regulatory factor 3 from Homo sapiens
Seq:
Struc: 		427 a.a.
226 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/nsb1001 Nat Struct Biol 10:922-927 (2003)
PubMed id: 14555995  
 
 
X-ray crystal structure of IRF-3 and its functional implications.
K.Takahasi, N.N.Suzuki, M.Horiuchi, M.Mori, W.Suhara, Y.Okabe, Y.Fukuhara, H.Terasawa, S.Akira, T.Fujita, F.Inagaki.
 
  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.
 
  Selected figure(s)  
 
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.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21200386 C.Li, L.Ma, and X.Chen (2010).
Interferon regulatory factor 3-CL, an isoform of IRF3, antagonizes activity of IRF3.
  Cell Mol Immunol, 8, 67-74.  
20930476 F.Inagaki, and F.Inagaki (2010).
[On the occasion of retirement from Graduate School of Pharmaceutical Sciences, Hokkaido University].
  Yakugaku Zasshi, 130, 1251-1262.  
20192994 P.S.Biswas, G.Bhagat, and A.B.Pernis (2010).
IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?
  Immunol Rev, 233, 79-96.  
20697158 P.S.Biswas, S.Gupta, E.Chang, L.Song, R.A.Stirzaker, J.K.Liao, G.Bhagat, and A.B.Pernis (2010).
Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice.
  J Clin Invest, 120, 3280-3295.  
19022341 J.A.Fleming, G.Song, Y.Choi, T.E.Spencer, and F.W.Bazer (2009).
Interferon regulatory factor 6 (IRF6) is expressed in the ovine uterus and functions as a transcriptional activator.
  Mol Cell Endocrinol, 299, 252-260.  
19211767 M.Nociari, O.Ocheretina, M.Murphy, and E.Falck-Pedersen (2009).
Adenovirus induction of IRF3 occurs through a binary trigger targeting Jun N-terminal kinase and TBK1 kinase cascades and type I interferon autocrine signaling.
  J Virol, 83, 4081-4091.  
19349300 P.Génin, R.Lin, J.Hiscott, and A.Civas (2009).
Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7.
  Mol Cell Biol, 29, 3435-3450.  
  18981097 H.Wang, C.A.Garcia, K.Rehani, C.Cekic, P.Alard, D.F.Kinane, T.Mitchell, and M.Martin (2008).
IFN-beta production by TLR4-stimulated innate immune cells is negatively regulated by GSK3-beta.
  J Immunol, 181, 6797-6802.  
18272581 J.F.Clément, A.Bibeau-Poirier, S.P.Gravel, N.Grandvaux, E.Bonneil, P.Thibault, S.Meloche, and M.J.Servant (2008).
Phosphorylation of IRF-3 on Ser 339 generates a hyperactive form of IRF-3 through regulation of dimerization and CBP association.
  J Virol, 82, 3984-3996.  
17924060 K.Ogawa, M.Funaba, and M.Tsujimoto (2008).
Suppression of NF-kappaB and IRF-1-induced transcription of the murine IL-12 p40 by transforming growth factor-beta Smad pathway in macrophages.
  Mol Cell Biochem, 308, 9.  
18303999 T.Tamura, H.Yanai, D.Savitsky, and T.Taniguchi (2008).
The IRF family transcription factors in immunity and oncogenesis.
  Annu Rev Immunol, 26, 535-584.  
18440553 W.Chen, H.Srinath, S.S.Lam, C.A.Schiffer, W.E.Royer, and K.Lin (2008).
Contribution of Ser386 and Ser396 to activation of interferon regulatory factor 3.
  J Mol Biol, 379, 251-260.  
18836453 W.Chen, S.S.Lam, H.Srinath, Z.Jiang, J.J.Correia, C.A.Schiffer, K.A.Fitzgerald, K.Lin, and W.E.Royer (2008).
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5.
  Nat Struct Mol Biol, 15, 1213-1220.
PDB code: 3dsh
17483521 A.I.Dragan, V.V.Hargreaves, E.N.Makeyeva, and P.L.Privalov (2007).
Mechanisms of activation of interferon regulator factor 3: the role of C-terminal domain phosphorylation in IRF-3 dimerization and DNA binding.
  Nucleic Acids Res, 35, 3525-3534.  
17399883 A.Paun, and P.M.Pitha (2007).
The IRF family, revisited.
  Biochimie, 89, 744-753.  
17560375 C.R.Escalante, E.Nistal-Villán, L.Shen, A.García-Sastre, and A.K.Aggarwal (2007).
Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer.
  Mol Cell, 26, 703-716.
PDB code: 2pi0
17526488 D.Panne, S.M.McWhirter, T.Maniatis, and S.C.Harrison (2007).
Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch.
  J Biol Chem, 282, 22816-22822.  
17599067 F.Ikeda, C.M.Hecker, A.Rozenknop, R.D.Nordmeier, V.Rogov, K.Hofmann, S.Akira, V.Dötsch, and I.Dikic (2007).
Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes.
  EMBO J, 26, 3451-3462.  
17395583 J.Hiscott (2007).
Triggering the innate antiviral response through IRF-3 activation.
  J Biol Chem, 282, 15325-15329.  
17502370 K.Ozato, P.Tailor, and T.Kubota (2007).
The interferon regulatory factor family in host defense: mechanism of action.
  J Biol Chem, 282, 20065-20069.  
17923090 X.Tang, J.S.Gao, Y.J.Guan, K.E.McLane, Z.L.Yuan, B.Ramratnam, and Y.E.Chin (2007).
Acetylation-dependent signal transduction for type I interferon receptor.
  Cell, 131, 93.  
17072332 J.Hiscott, T.L.Nguyen, M.Arguello, P.Nakhaei, and S.Paz (2006).
Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses.
  Oncogene, 25, 6844-6867.  
16979567 K.Honda, A.Takaoka, and T.Taniguchi (2006).
Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.
  Immunity, 25, 349-360.  
15743772 A.Caillaud, A.G.Hovanessian, D.E.Levy, and I.J.Marié (2005).
Regulatory serine residues mediate phosphorylation-dependent and phosphorylation-independent activation of interferon regulatory factor 7.
  J Biol Chem, 280, 17671-17677.  
16154084 B.Y.Qin, C.Liu, H.Srinath, S.S.Lam, J.J.Correia, R.Derynck, and K.Lin (2005).
Crystal structure of IRF-3 in complex with CBP.
  Structure, 13, 1269-1277.  
16154077 J.Hiscott, and R.Lin (2005).
IRF-3 releases its inhibitions.
  Structure, 13, 1235-1236.
PDB code: 1zoq
15919920 K.Brzózka, S.Finke, and K.K.Conzelmann (2005).
Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3.
  J Virol, 79, 7673-7681.  
15688040 M.Lohoff, and T.W.Mak (2005).
Roles of interferon-regulatory factors in T-helper-cell differentiation.
  Nat Rev Immunol, 5, 125-135.  
15849753 M.Nakanishi, Y.Goto, and Y.Kitade (2005).
2-5A induces a conformational change in the ankyrin-repeat domain of RNase L.
  Proteins, 60, 131-138.  
15764595 Y.Obata, K.Yamamoto, M.Miyazaki, K.Shimotohno, S.Kohno, and T.Matsuyama (2005).
Role of cyclophilin B in activation of interferon regulatory factor-3.
  J Biol Chem, 280, 18355-18360.  
15367631 B.R.tenOever, S.Sharma, W.Zou, Q.Sun, N.Grandvaux, I.Julkunen, H.Hemmi, M.Yamamoto, S.Akira, W.C.Yeh, R.Lin, and J.Hiscott (2004).
Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity.
  J Virol, 78, 10636-10649.  
15510218 D.Panne, T.Maniatis, and S.C.Harrison (2004).
Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.
  EMBO J, 23, 4384-4393.
PDB code: 1t2k
15523474 J.Hiscott (2004).
Another detour on the Toll road to the interferon antiviral response.
  Nat Struct Mol Biol, 11, 1028-1030.  
14703513 M.Mori, M.Yoneyama, T.Ito, K.Takahashi, F.Inagaki, and T.Fujita (2004).
Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation.
  J Biol Chem, 279, 9698-9702.  
14555996 B.Y.Qin, C.Liu, S.S.Lam, H.Srinath, R.Delston, J.J.Correia, R.Derynck, and K.Lin (2003).
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation.
  Nat Struct Biol, 10, 913-921.
PDB code: 1qwt
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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