PDBsum entry 1bft

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protein Protein-protein interface(s) links
Transcription factor PDB id
Protein chains
101 a.a. *
Waters ×267
* Residue conservation analysis
PDB id:
Name: Transcription factor
Title: Structure of nf-kb p50 homodimer bound to a kb site
Structure: Nuclear factor nf-kappa-b p65. Chain: a, b. Fragment: dimerization domain
Source: Mus musculus. House mouse. Organism_taxid: 10090
Biol. unit: Tetramer (from PQS)
2.00Å     R-factor:   0.204     R-free:   0.294
Authors: D.B.Huang,T.Huxford,Y.Q.Chen,G.Ghosh
Key ref:
D.B.Huang et al. (1997). The role of DNA in the mechanism of NFkappaB dimer formation: crystal structures of the dimerization domains of the p50 and p65 subunits. Structure, 5, 1427-1436. PubMed id: 9384558 DOI: 10.1016/S0969-2126(97)00293-1
12-Sep-97     Release date:   28-Jan-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q04207  (TF65_MOUSE) -  Transcription factor p65
549 a.a.
101 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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(97)00293-1 Structure 5:1427-1436 (1997)
PubMed id: 9384558  
The role of DNA in the mechanism of NFkappaB dimer formation: crystal structures of the dimerization domains of the p50 and p65 subunits.
D.B.Huang, T.Huxford, Y.Q.Chen, G.Ghosh.
BACKGROUND: Members of the rel/NFkappaB family of transcription factors play a vital role in the regulation of rapid cellular responses, such as those required to fight infection or react to cellular stress. Members of this family of proteins form homo- and heterodimers with differing affinities for dimerization. They share a structural motif known as the rel homology region (RHR), the C-terminal one third of which mediates protein dimerization. Crystal structures of the rel/NFkappaB family members p50 and p65 in their DNA-bound homodimeric form have been solved. These structures showed that the residues from the dimerization domains of both p50 and p65 participate in DNA binding and that the DNA-protein and protein dimerization surfaces form one continuous overlapping interface. We desired to investigate the contribution of DNA to NFkappaB dimerization and to identify the mechanism for the selective association of rel/NFkappaB family peptides into transcriptionally active dimers. RESULTS: We report here the crystal structures of the dimerization domains of murine p50 and p65 at 2.2 A and 2.0 A resolution, respectively. A comparison of these two structures suggests that conservative amino acid changes at three positions are responsible for the differences in their dimer interfaces. The presence of the target DNA does not change the dimer interface of either protein in any significant manner. CONCLUSIONS: These two structures suggest that the rel/NFkappaB family of transcription factors use only a few conservative changes in their amino acid sequences to form a host of dimers with varying affinities for dimerization. Amino acids at positions corresponding to 254, 267, and 307 of murine p50, function as primary determinants for the observed differences in dimerization affinity. The DNA-contacting charged amino acid sidechains from the dimerization domains are held in a similar conformation in both the DNA-bound and free states, therefore, no major structural rearrangement is required to bring these residues into contact with the DNA.
  Selected figure(s)  
Figure 2.
Figure 2. Comparison of the contribution of residues Tyr267 and Asp254 of p50 and the homologous pair, Phe213 and Asn200 of p65, to their respective dimer interfaces. The different monomers are indicated by the letters A and B preceding the amino acid number. (a) In p50, Tyr267 from monomer A (cyan) and monomer B (green) participate in hydrogen-bonding networks (red dashed lines) which direct the two Asp254 residues towards each other in a dimer-weakening interaction. (b) In p65, the two Phe213 residues fail to form the extensive hydrogen-bonding networks of the homologous Tyr267 in p50. The weaker dimer interface allows the polar Asn200 residues of monomer A (cyan) and B (green) the freedom to move away from each other.
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1427-1436) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21460456 E.Krissinel (2011).
Macromolecular complexes in crystals and solutions.
  Acta Crystallogr D Biol Crystallogr, 67, 376-385.  
19421996 E.Krissinel (2010).
Crystal contacts as nature's docking solutions.
  J Comput Chem, 31, 133-143.  
  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.  
18433497 S.Raza, K.A.Robertson, P.A.Lacaze, D.Page, A.J.Enright, P.Ghazal, and T.C.Freeman (2008).
A logic-based diagram of signalling pathways central to macrophage activation.
  BMC Syst Biol, 2, 36.  
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.  
17072323 A.Hoffmann, G.Natoli, and G.Ghosh (2006).
Transcriptional regulation via the NF-kappaB signaling module.
  Oncogene, 25, 6706-6716.  
16154093 D.B.Huang, D.Vu, and G.Ghosh (2005).
NF-kappaB RelB forms an intertwined homodimer.
  Structure, 13, 1365-1373.
PDB codes: 1zk9 1zka
15296742 D.Y.Chirgadze, M.Demydchuk, M.Becker, S.Moran, and M.Paoli (2004).
Snapshot of protein structure evolution reveals conservation of functional dimerization through intertwined folding.
  Structure, 12, 1489-1494.
PDB codes: 1u36 1u3j 1u3y 1u3z 1u41 1u42
12874295 H.J.Maier, R.Marienfeld, T.Wirth, and B.Baumann (2003).
Critical role of RelB serine 368 for dimerization and p100 stabilization.
  J Biol Chem, 278, 39242-39250.  
11967310 A.S.Liss, and H.R.Bose (2002).
Mutational analysis of the v-Rel dimerization interface reveals a critical role for v-Rel homodimers in transformation.
  J Virol, 76, 4928-4939.  
11232330 T.Huxford, S.Malek, and G.Ghosh (1999).
Structure and mechanism in NF-kappa B/I kappa B signaling.
  Cold Spring Harb Symp Quant Biol, 64, 533-540.  
9738011 S.Malek, T.Huxford, and G.Ghosh (1998).
Ikappa Balpha functions through direct contacts with the nuclear localization signals and the DNA binding sequences of NF-kappaB.
  J Biol Chem, 273, 25427-25435.  
9437432 Y.Q.Chen, S.Ghosh, and G.Ghosh (1998).
A novel DNA recognition mode by the NF-kappa B p65 homodimer.
  Nat Struct Biol, 5, 67-73.
PDB codes: 1ram 2ram
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