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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
1gji
Jmol
Contents
Protein chains
275 a.a. *
DNA/RNA
* Residue conservation analysis
PDB id:
1gji
Name: Transcription/DNA
Title: Crystal structure of c-rel bound to DNA
Structure: Il-2 cd28re DNA. Chain: c. Engineered: yes. Il-2 cd28re DNA. Chain: d. Engineered: yes. C-rel proto-oncogene protein. Chain: a, b. Fragment: rel homology region.
Source: Synthetic: yes. Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Octamer (from PQS)
Resolution:
2.85Å     R-factor:   0.227     R-free:   0.279
Authors: D.B.Huang,Y.Q.Chen,M.Ruetsche,C.B.Phelps,G.Ghosh
Key ref:
D.B.Huang et al. (2001). X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2. Structure, 9, 669-678. PubMed id: 11587641 DOI: 10.1016/S0969-2126(01)00635-9
Date:
30-May-01     Release date:   30-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16236  (REL_CHICK) -  Proto-oncogene c-Rel
Seq:
Struc: 		 
Seq:
Struc: 		598 a.a.
275 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   2 terms 
  Biochemical function     transcription factor activity     1 term  

 

 
DOI no: 10.1016/S0969-2126(01)00635-9 Structure 9:669-678 (2001)
PubMed id: 11587641  
 
 
X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28 response element of IL-2.
D.B.Huang, Y.Q.Chen, M.Ruetsche, C.B.Phelps, G.Ghosh.
 
  ABSTRACT  
 
BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family transcription factor that plays a critical role in lymphoid cell development and mediates CD28-induced expression of interleukin 2 (IL-2). The CD28 response element (CD28RE) in the IL-2 enhancer is nonameric and similar to the kappaB DNA target sites recognized by p65 homodimers. RESULTS: We have determined and refined the X-ray crystal structure of the c-Rel homodimer complexed to the CD28RE DNA site, 5'-AGAAATTCC-3', to 2.85 A resolution. The c-Rel homodimer binds CD28RE in a mode similar to that observed in the p65/IL-8 kappaB crystallographic complex. Binding studies reveal that the c-Rel homodimer recognizes the CD28RE with higher affinity as compared to other canonical kappaB sequences despite the nonconsensus A:T base pair at the 5' end of the CD28RE. Preferential recognition of the CD28RE by c-Rel results from the direct contacts between the protein and the DNA as well as intrasubunit interactions between the beta(f)-beta(g) loop in the dimerization domain and the DNA-contacting loop L1 of the N-terminal domain. Not only do these loops have different conformations in other Rel/DNA crystallographic complexes, but they also contain two of the five oncogenic point mutations found in v-Rel. CONCLUSIONS: The current structure indicates that a non-DNA-contacting loop in the dimerization domain and the DNA-contacting loop L1 may play critical roles in defining affinity and specificity. Two amino acid changes in these segments may account for the differential DNA binding by v-Rel as compared to that of c-Rel.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Location of v-Rel Mutations(a) A backbone trace of a c-Rel monomer interacting with DNA shows the location of the five amino acid residues that are mutated in v-Rel. The L1 and bf-bg loops are colored magenta and yellow, respectively.(b) van der Waals contacts (dotted spheres) in the N-terminal domain of c-Rel; these contacts could be disrupted by the Met20Thr mutation in v-Rel. The key Met residue's surface is highlighted in magenta.(c) Diagram of 2F[o] -F[c] electron density (contoured at 1 s) for residues involved in interdomain contacts between the L1 and bf-bg loops in c-Rel. Hydrogen bonds are represented by dashed lines

 
  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 669-678) copyright 2001.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19098713 A.J.Fusco, D.B.Huang, D.Miller, V.Y.Wang, D.Vu, and G.Ghosh (2009).
NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes.
  EMBO Rep, 10, 152-159.  
19806632 L.Piccagli, E.Fabbri, M.Borgatti, N.Bianchi, V.Bezzerri, I.Mancini, E.Nicolis, C.M.Dechecchi, I.Lampronti, G.Cabrini, and R.Gambari (2009).
Virtual Screening against p50 NF-kappaB Transcription Factor for the Identification of Inhibitors of the NF-kappaB-DNA Interaction and Expression of NF-kappaB Upregulated Genes.
  ChemMedChem, 4, 2024-2033.  
18653524 C.Mura, and J.A.McCammon (2008).
Molecular dynamics of a kappaB DNA element: base flipping via cross-strand intercalative stacking in a microsecond-scale simulation.
  Nucleic Acids Res, 36, 4941-4955.  
18626097 H.J.Ahn, C.M.Hernandez, J.M.Levenson, F.D.Lubin, H.C.Liou, and J.D.Sweatt (2008).
c-Rel, an NF-kappaB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation.
  Learn Mem, 15, 539-549.  
18695674 J.R.Leeman, M.A.Weniger, T.F.Barth, and T.D.Gilmore (2008).
Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL.
  Oncogene, 27, 6770-6781.  
  18768853 L.Guo, J.F.Urban, J.Zhu, and W.E.Paul (2008).
Elevating calcium in Th2 cells activates multiple pathways to induce IL-4 transcription and mRNA stabilization.
  J Immunol, 181, 3984-3993.  
17785540 R.R.Copley, M.Totrov, J.Linnell, S.Field, J.Ragoussis, and I.A.Udalova (2007).
Functional conservation of Rel binding sites in drosophilid genomes.
  Genome Res, 17, 1327-1335.  
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
15677444 R.Fagerlund, L.Kinnunen, M.Köhler, I.Julkunen, and K.Melén (2005).
NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4.
  J Biol Chem, 280, 15942-15951.  
16166378 S.Sanjabi, K.J.Williams, S.Saccani, L.Zhou, A.Hoffmann, G.Ghosh, S.Gerondakis, G.Natoli, and S.T.Smale (2005).
A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation.
  Genes Dev, 19, 2138-2151.  
15102445 G.Ghosh, D.B.Huang, and T.Huxford (2004).
Molecular mimicry of the NF-kappaB DNA target site by a selected RNA aptamer.
  Curr Opin Struct Biol, 14, 21-27.  
15606917 K.A.Smith (2004).
The quantal theory of how the immune system discriminates between "self and non-self"
  Med Immunol, 3, 3.  
12588973 B.Rayet, Y.Fan, and C.Gélinas (2003).
Mutations in the v-Rel transactivation domain indicate altered phosphorylation and identify a subset of NF-kappaB-regulated cell death inhibitors important for v-Rel transforming activity.
  Mol Cell Biol, 23, 1520-1533.  
11839497 A.J.Warren (2002).
Eukaryotic transcription factors.
  Curr Opin Struct Biol, 12, 107-114.  
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.  
11970948 B.Berkowitz, D.B.Huang, F.E.Chen-Park, P.B.Sigler, and G.Ghosh (2002).
The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the interferon beta -kappa B site.
  J Biol Chem, 277, 24694-24700.
PDB codes: 1le5 1le9
  12005436 C.R.Escalante, L.Shen, D.Thanos, and A.K.Aggarwal (2002).
Structure of NF-kappaB p50/p65 heterodimer bound to the PRDII DNA element from the interferon-beta promoter.
  Structure, 10, 383-391.
PDB code: 2i9t
11983155 S.Ghosh, and M.Karin (2002).
Missing pieces in the NF-kappaB puzzle.
  Cell, 109, S81-S96.  
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 codes are shown on the right.