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PDBsum entry 2i9t

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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
2i9t
Jmol
Contents
Protein chains
275 a.a. *
312 a.a. *
DNA/RNA
Waters ×21
* Residue conservation analysis
PDB id:
2i9t
Name: Transcription/DNA
Title: Structure of nf-kb p65-p50 heterodimer bound to prdii element of b-interferon promoter
Structure: 5'- d( Ap Gp Tp Gp Gp Gp Ap Ap Ap Tp Tp Cp Cp Tp Cp Tp G)-3'. Chain: c. Engineered: yes. Other_details: prdii DNA element. 5'- d( Cp Ap Gp Ap Gp Gp Ap Ap Tp Tp Tp Cp Cp Cp Ap Cp T)-3'. Chain: d. Engineered: yes.
Source: Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Gene: rela, nfkb3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: nfkb1.
Resolution:
2.80Å     R-factor:   0.233     R-free:   0.288
Authors: C.R Escalante,L.Shen,D.Thanos,A.K.Aggarwal
Key ref:
C.R.Escalante et al. (2002). Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter. Structure, 10, 383-391. PubMed id: 12005436 DOI: 10.1016/S0969-2126(02)00723-2
Date:
06-Sep-06     Release date:   06-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
Seq:
Struc:
 
Seq:
Struc:
549 a.a.
275 a.a.*
Protein chain
Pfam   ArchSchema ?
P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit
Seq:
Struc:
 
Seq:
Struc:
971 a.a.
312 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     sequence-specific DNA binding transcription factor activity     1 term  

 

 
DOI no: 10.1016/S0969-2126(02)00723-2 Structure 10:383-391 (2002)
PubMed id: 12005436  
 
 
Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
C.R.Escalante, L.Shen, D.Thanos, A.K.Aggarwal.
 
  ABSTRACT  
 
Upon viral infection, NF-kappaB translocates to the nucleus and activates the IFN-beta gene by binding to the PRDII element. Strikingly, NF-kappaB loses its ability to activate the IFN-beta gene when the PRDII element is substituted by closely related sites. We report here the crystal structure of NF-kappaB p50/p65 heterodimer bound to the PRDII element from the IFN-beta promoter. The structure reveals an unexpected alteration in configuration, in which the p50 specificity domain moves by as much as approximately 9 A when compared to NF-kappaB heterodimer bound to the immunoglobulin kappaB site (Ig-kappaB) while maintaining the same base-specific contacts with the DNA. Taken together, the structure offers new insights into the allosteric effects of closely related DNA sites on the configuration of NF-kappaB and its transcriptional selectivity.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Overall View of the Structure
(A) Ribbon diagram of the p65/p50 heterodimer bound to the PRDII element, viewed down the DNA helical axis. The p50 subunit is shown in blue and the p65 subunit in red. The DNA is shown in gold. The secondary elements, loops, and N and C termini are labeled.
(B) Stereo representation of a Cα trace of the complex, with every twentieth residue labeled. Figure 2. Overall View of the Structure(A) Ribbon diagram of the p65/p50 heterodimer bound to the PRDII element, viewed down the DNA helical axis. The p50 subunit is shown in blue and the p65 subunit in red. The DNA is shown in gold. The secondary elements, loops, and N and C termini are labeled.(B) Stereo representation of a Cα trace of the complex, with every twentieth residue labeled.
Figure 5.
Figure 5. Comparison of van der Waals Interactions between Tyr57 and the Inner DNA Bases
(A) In the NF-κB[50/65]-PRDII structure, Tyr57 is shown interacting with the methyl groups of adjacent A:T base pairs.
(B) In the NF-κB[50/65]-Ig structure, the thymine of the single A:T base pair rolls and twists out of plane. Figure 5. Comparison of van der Waals Interactions between Tyr57 and the Inner DNA Bases(A) In the NF-κB[50/65]-PRDII structure, Tyr57 is shown interacting with the methyl groups of adjacent A:T base pairs.(B) In the NF-κB[50/65]-Ig structure, the thymine of the single A:T base pair rolls and twists out of plane.
 
  The above figures are reprinted by permission from Cell Press: Structure (2002, 10, 383-391) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472811 B.Manavalan, R.Govindaraj, G.Lee, and S.Choi (2011).
Molecular modeling-based evaluation of dual function of IκBζ ankyrin repeat domain in toll-like receptor signaling.
  J Mol Recognit, 24, 597-607.  
20504937 J.Jiao, H.Guan, A.M.Lippa, and R.P.Ricciardi (2010).
The N terminus of adenovirus type 12 E1A inhibits major histocompatibility complex class I expression by preventing phosphorylation of NF-kappaB p65 Ser276 through direct binding.
  J Virol, 84, 7668-7674.  
19720834 C.R.Plumlee, C.Lee, A.A.Beg, T.Decker, H.A.Shuman, and C.Schindler (2009).
Interferons direct an effective innate response to Legionella pneumophila infection.
  J Biol Chem, 284, 30058-30066.  
19201872 F.L.Sinquett, R.L.Dryer, V.Marcelli, A.Batheja, and L.R.Covey (2009).
Single nucleotide changes in the human Igamma1 and Igamma4 promoters underlie different transcriptional responses to CD40.
  J Immunol, 182, 2185-2193.  
19683540 J.C.Stroud, A.Oltman, A.Han, D.L.Bates, and L.Chen (2009).
Structural basis of HIV-1 activation by NF-kappaB--a higher-order complex of p50:RelA bound to the HIV-1 LTR.
  J Mol Biol, 393, 98.
PDB code: 3gut
  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.  
18206362 D.Panne (2008).
The enhanceosome.
  Curr Opin Struct Biol, 18, 236-242.  
19027345 F.Weber, and A.Mirazimi (2008).
Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis.
  Cytokine Growth Factor Rev, 19, 395-404.  
17959673 H.Guan, J.Jiao, and R.P.Ricciardi (2008).
Tumorigenic adenovirus type 12 E1A inhibits phosphorylation of NF-kappaB by PKAc, causing loss of DNA binding and transactivation.
  J Virol, 82, 40-48.  
17303559 A.V.Tsytsykova, J.V.Falvo, M.Schmidt-Supprian, G.Courtois, D.Thanos, and A.E.Goldfeld (2007).
Post-induction, stimulus-specific regulation of tumor necrosis factor mRNA expression.
  J Biol Chem, 282, 11629-11638.  
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
17574024 D.Panne, T.Maniatis, and S.C.Harrison (2007).
An atomic model of the interferon-beta enhanceosome.
  Cell, 129, 1111-1123.
PDB codes: 2o61 2o6g
16336179 A.S.Romanenkov, A.A.Ustyugov, T.S.Zatsepin, A.A.Nikulova, I.V.Kolesnikov, V.G.Metelev, T.S.Oretskaya, and E.A.Kubareva (2005).
Analysis of DNA-protein interactions in complexes of transcription factor NF-kappaB with DNA.
  Biochemistry (Mosc), 70, 1212-1222.  
15051810 R.Crinelli, M.Bianchi, L.Gentilini, L.Palma, M.D.Sørensen, T.Bryld, R.B.Babu, K.Arar, J.Wengel, and M.Magnani (2004).
Transcription factor decoy oligonucleotides modified with locked nucleic acids: an in vitro study to reconcile biostability with binding affinity.
  Nucleic Acids Res, 32, 1874-1885.  
15315758 T.H.Leung, A.Hoffmann, and D.Baltimore (2004).
One nucleotide in a kappaB site can determine cofactor specificity for NF-kappaB dimers.
  Cell, 118, 453-464.  
14532125 A.Hoffmann, T.H.Leung, and D.Baltimore (2003).
Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities.
  EMBO J, 22, 5530-5539.  
12949493 M.J.Giffin, J.C.Stroud, D.L.Bates, K.D.von Koenig, J.Hardin, and L.Chen (2003).
Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.
  Nat Struct Biol, 10, 800-806.
PDB code: 1p7h
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.