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protein Protein-protein interface(s) links
DNA binding protein PDB id
1oy3
Jmol
Contents
Protein chains
135 a.a. *
112 a.a. *
220 a.a. *
Waters ×248
* Residue conservation analysis
PDB id:
1oy3
Name: DNA binding protein
Title: Crystal structure of an ikbbeta/nf-kb p65 homodimer complex
Structure: Transcription factor p65. Chain: c, b. Fragment: p65 dimerization domain. Synonym: nuclear factor nf-kappa-b p65 subunit. Engineered: yes. Transcription factor inhibitor i-kappa-b-beta. Chain: d. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: rela or nfkb3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Trimer (from PQS)
Resolution:
2.05Å     R-factor:   0.218     R-free:   0.247
Authors: S.Malek,D.B.Huang,T.Huxford,S.Ghosh,G.Ghosh
Key ref:
S.Malek et al. (2003). X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex. J Biol Chem, 278, 23094-23100. PubMed id: 12686541 DOI: 10.1074/jbc.M301022200
Date:
03-Apr-03     Release date:   20-May-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
Seq:
Struc: 		 
Seq:
Struc: 		549 a.a.
135 a.a.
Protein chain
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
Seq:
Struc: 		 
Seq:
Struc: 		549 a.a.
112 a.a.
Protein chain
Pfam   ArchSchema ?
Q60778  (IKBB_MOUSE) -  NF-kappa-B inhibitor beta
Seq:
Struc: 		359 a.a.
220 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     transcription factor activity     1 term  

 

 
DOI no: 10.1074/jbc.M301022200 J Biol Chem 278:23094-23100 (2003)
PubMed id: 12686541  
 
 
X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex.
S.Malek, D.B.Huang, T.Huxford, S.Ghosh, G.Ghosh.
 
  ABSTRACT  
 
We report the crystal structure of a murine IkappaBbeta x NF-kappaB p65 homodimer complex. Crystallographic models were determined for two triclinic crystalline systems and refined against data at 2.5 and 2.1 A. The overall complex structure is similar to that of the IkappaBalpha.NF-kappaB p50/p65 heterodimer complex. One NF-kappaB p65 subunit nuclear localization signal clearly contacts IkappaBbeta, whereas a homologous segment from the second subunit of the homodimer is mostly solvent-exposed. The unique 47-amino acid insertion between ankyrin repeats three and four of IkappaBbeta is mostly disordered in the structure. Primary sequence analysis and differences in the mode of binding at the IkappaBbeta sixth ankyrin repeat and NF-kappaB p65 homodimer suggest a model for nuclear IkappaBbeta.NF-kappaB.DNA ternary complex formation. These unique structural features of IkappaBbeta may contribute to its ability to mediate persistent NF-kappaB activation.
 
  Selected figure(s)  
 
Figure 4.
FIG. 4. Comparison of the interactions between the sixth ankyrin repeat of I B and I B and the p65 subunit A. A, superposition of the p65 subunit A dimerization domain from the two I B·NF- B complexes reveals the overall similarity in position and fold of the complex-associated I B and I B . Color scheme is consistent with previous figures, except that the p65 subunit from the I B ·NF- B complex structure is depicted in pink. Ankyrin repeats are numbered. One noticeable difference (enclosed within the dashed black box) is that the sixth ankyrin repeat of I B occupies a position at a greater distance from p65 than does the corresponding segment of I B . B, close up stereoview of the boxed area from A. Arg260 and Trp258 are labeled as reference points. 		Figure 5.
FIG. 5. To model the I B ·p65·DNA ternary complex, atomic coordinates from the p65·interleukin-8- B DNA complex were used (54). The dimerization domains of p65 were superposed on to the similar domains from the present structure. The second p65 NLS has been removed from this model. Three arginine side chains that are positioned near the interleukin-8 B DNA (gray cpk model) from I B , Arg275, Arg284, and Arg294, are rendered as ball-and-stick models.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 23094-23100) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21135870 C.Zheng, Q.Yin, and H.Wu (2011).
Structural studies of NF-κB signaling.
  Cell Res, 21, 183-195.  
21158742 T.Valovka, and M.O.Hottiger (2011).
p65 controls NF-κB activity by regulating cellular localization of IκBβ.
  Biochem J, 434, 253-263.  
21203422 B.Manavalan, S.Basith, Y.M.Choi, G.Lee, and S.Choi (2010).
Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis.
  PLoS One, 5, e15782.  
20521980 C.H.Chang, C.Y.Chen, J.Y.Chiou, R.Y.Peng, and C.H.Peng (2010).
Astaxanthine secured apoptotic death of PC12 cells induced by beta-amyloid peptide 25-35: its molecular action targets.
  J Med Food, 13, 548-556.  
20975741 H.Kamata, Y.Tsuchiya, and T.Asano (2010).
IκBβ is a positive and negative regulator of NF-κB activity during inflammation.
  Cell Res, 20, 1178-1180.  
20740013 P.Rao, M.S.Hayden, M.Long, M.L.Scott, A.P.West, D.Zhang, A.Oeckinghaus, C.Lynch, A.Hoffmann, D.Baltimore, and S.Ghosh (2010).
IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response.
  Nature, 466, 1115-1119.  
20553411 S.Wu, and L.Tong (2010).
Differential signaling circuits in regulation of ultraviolet C light-induced early- and late-phase activation of NF-κB.
  Photochem Photobiol, 86, 995-999.  
  20066092 A.Oeckinghaus, and S.Ghosh (2009).
The NF-kappaB family of transcription factors and its regulation.
  Cold Spring Harbor Perspect Biol, 1, a000034.  
19224334 C.F.László, and S.Wu (2009).
Old target new approach: an alternate NF-kappaB activation pathway via translation inhibition.
  Mol Cell Biochem, 328, 9.  
19655301 C.Gasparini, B.M.Foxwell, and M.Feldmann (2009).
RelB/p50 regulates CCL19 production, but fails to promote human DC maturation.
  Eur J Immunol, 39, 2215-2223.  
19887633 S.Bergqvist, V.Alverdi, B.Mengel, A.Hoffmann, G.Ghosh, and E.A.Komives (2009).
Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha.
  Proc Natl Acad Sci U S A, 106, 19328-19333.  
  20066103 T.Huxford, and G.Ghosh (2009).
A structural guide to proteins of the NF-kappaB signaling module.
  Cold Spring Harbor Perspect Biol, 1, a000075.  
18627520 C.F.László, and S.Wu (2008).
Mechanism of UV-induced IkappaBalpha-independent activation of NF-kappaB.
  Photochem Photobiol, 84, 1564-1568.  
  19046417 M.Coiras, M.R.Lopez-Huertas, E.Mateos, and J.Alcami (2008).
Caspase-3-mediated cleavage of p65/RelA results in a carboxy-terminal fragment that inhibits IkappaBalpha and enhances HIV-1 replication in human T lymphocytes.
  Retrovirology, 5, 109.  
18565540 S.C.Sue, C.Cervantes, E.A.Komives, and H.J.Dyson (2008).
Transfer of flexibility between ankyrin repeats in IkappaB* upon formation of the NF-kappaB complex.
  J Mol Biol, 380, 917-931.  
17174335 D.U.Ferreiro, C.F.Cervantes, S.M.Truhlar, S.S.Cho, P.G.Wolynes, and E.A.Komives (2007).
Stabilizing IkappaBalpha by "consensus" design.
  J Mol Biol, 365, 1201-1216.  
17445259 R.García-Román, J.I.Pérez-Carreón, A.Márquez-Quiñones, M.E.Salcido-Neyoy, and S.Villa-Treviño (2007).
Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis.
  J Carcinog, 6, 5.  
17452470 S.K.Moon, J.I.Woo, H.Y.Lee, R.Park, J.Shimada, H.Pan, R.Gellibolian, and D.J.Lim (2007).
Toll-like receptor 2-dependent NF-kappaB activation is involved in nontypeable Haemophilus influenzae-induced monocyte chemotactic protein 1 up-regulation in the spiral ligament fibrocytes of the inner ear.
  Infect Immun, 75, 3361-3372.  
17072323 A.Hoffmann, G.Natoli, and G.Ghosh (2006).
Transcriptional regulation via the NF-kappaB signaling module.
  Oncogene, 25, 6706-6716.  
15899873 A.S.Chung, Y.J.Guan, Z.L.Yuan, J.E.Albina, and Y.E.Chin (2005).
Ankyrin repeat and SOCS box 3 (ASB3) mediates ubiquitination and degradation of tumor necrosis factor receptor II.
  Mol Cell Biol, 25, 4716-4726.  
15969767 D.H.Dreyfus, M.Nagasawa, E.W.Gelfand, and L.Y.Ghoda (2005).
Modulation of p53 activity by IkappaBalpha: evidence suggesting a common phylogeny between NF-kappaB and p53 transcription factors.
  BMC Immunol, 6, 12.  
15923614 E.Hertlein, J.Wang, K.J.Ladner, N.Bakkar, and D.C.Guttridge (2005).
RelA/p65 regulation of IkappaBbeta.
  Mol Cell Biol, 25, 4956-4968.  
16356863 H.C.Chang, K.Tan, J.Ouyang, E.Parisini, J.H.Liu, Y.Le, X.Wang, E.L.Reinherz, and J.H.Wang (2005).
Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer.
  Immunity, 23, 661-671.
PDB code: 2atp
15152081 L.K.Mosavi, T.J.Cammett, D.C.Desrosiers, and Z.Y.Peng (2004).
The ankyrin repeat as molecular architecture for protein recognition.
  Protein Sci, 13, 1435-1448.  
15143182 S.O'Connor, S.D.Shumway, I.J.Amanna, C.E.Hayes, and S.Miyamoto (2004).
Regulation of constitutive p50/c-Rel activity via proteasome inhibitor-resistant IkappaBalpha degradation in B cells.
  Mol Cell Biol, 24, 4895-4908.  
15240830 S.Zelivianski, R.Glowacki, and M.F.Lin (2004).
Transcriptional activation of the human prostatic acid phosphatase gene by NF-kappaB via a novel hexanucleotide-binding site.
  Nucleic Acids Res, 32, 3566-3580.  
15211579 X.Lu, P.Farmer, J.Rubin, and M.S.Nanes (2004).
Integration of the NfkappaB p65 subunit into the vitamin D receptor transcriptional complex: identification of p65 domains that inhibit 1,25-dihydroxyvitamin D3-stimulated transcription.
  J Cell Biochem, 92, 833-848.  
15024091 Y.Chen, S.Vallee, J.Wu, D.Vu, J.Sondek, and G.Ghosh (2004).
Inhibition of NF-kappaB activity by IkappaBbeta in association with kappaB-Ras.
  Mol Cell Biol, 24, 3048-3056.  
14636585 C.Schmidt, B.Peng, Z.Li, G.M.Sclabas, S.Fujioka, J.Niu, M.Schmidt-Supprian, D.B.Evans, J.L.Abbruzzese, and P.J.Chiao (2003).
Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation.
  Mol Cell, 12, 1287-1300.  
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.