PDBsum entry: 1le9

Transcription/DNA

PDB id: 1le9

Contents

Protein chains

273 a.a. *

312 a.a. *

DNA/RNA

* Residue conservation analysis

PDB id:

1le9

Name:

Transcription/DNA

Title:

Crystal structure of a nf-kb heterodimer bound to the ig/HIV-kb siti

Structure:

5'-d( Tp Gp Gp Gp Ap Cp Tp Tp Tp Cp Cp T)-3'. Chain: c, g. Engineered: yes. Other_details: ig/hiv2-kb DNA. 5'-d( Ap Ap Gp Gp Ap Ap Ap Gp Tp Cp Cp C)-3'. Chain: d, h. Engineered: yes. Other_details: ig/hiv2-kb DNA. Nuclear factor nf-kappa-b p65 subunit.

Source:

Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Gene: rela. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: nfkb1.

Biol. unit:

Tetramer (from PQS)

Resolution:

3.00Å R-factor: 0.249 R-free: 0.305

Authors:

B.Benjamin,D.B.Huang,F.E.Chen-Park,P.B.Sigler,G.Ghosh

Key ref:

B.Berkowitz et al. (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. PubMed id: 11970948 DOI: 10.1074/jbc.M200006200

Date:

09-Apr-02 Release date: 15-Apr-03

Protein chains

Q04207  (TF65_MOUSE) -  Transcription factor p65

Seq: 549 a.a.

Struc: 273 a.a.*

Protein chains

P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit

Seq: 971 a.a.

Struc: 312 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription (2 terms)
• Biochemical function: transcription factor activity (1 term)

DOI no: 10.1074/jbc.M200006200

J Biol Chem 277:24694-24700 (2002)

PubMed id: 11970948

The x-ray crystal structure of the NF-kappa B p50.p65 heterodimer bound to the interferon beta -kappa B site.

B.Berkowitz, D.B.Huang, F.E.Chen-Park, P.B.Sigler, G.Ghosh.

ABSTRACT

We have determined the x-ray crystal structure of the transcription factor NF-kappaB p50.p65 heterodimer complexed to kappaB DNA from the cytokine interferon beta enhancer (IFNbeta-kappaB). To better understand how the binding modes of NF-kappaB on its two best studied DNA targets might contribute to promoter-specific transcription, this structure is compared with the previously determined complex crystal structure containing NF-kappaB bound to the Ig kappa light chain gene enhancer as well as to a second NF-kappaB.Ig kappa light chain gene enhancer complex also reported in this paper. The global binding modes of all NF-kappaB.DNA complex structures are similar, although crystal-packing interactions lead to differences between identical complexes of the same crystallographic asymmetric unit. An extensive network of stacked amino acid side chains that contribute to base-specific DNA contacts is conserved among the three complexes. Consistent with earlier reports, however, the IFNbeta-kappaB DNA is bent significantly less by NF-kappaB than is the Ig kappa light chain gene enhancer. This and other small structural changes may play a role in explaining why NF-kappaB-directed transcription is sensitive to the context of specific promoters. The precise molecular mechanism behind the involvement of the high mobility group protein I(Y) in interferon beta enhanceosome formation remains elusive.

Selected figure(s)

Figure 1.
Fig. 1. Schematic of the Rel homology region p50 and p65 and B DNA sequences. a, the RHR of p50 and p65 contain amino- and carboxyl-terminal domains ( CTD) linked by a short linker sequence. The numbering corresponds to murine p50 (depicted in yellow) and murine p65 (shown in green). b, the B DNA sequences referred to in this study are shown. The structures of NF- B co-crystals with PRDII (IFN - B) and Ig/HIV-2 sequences are described in detail. The Ig/HIV-1 sequence was used in our previous study (8). Shown for comparison are the uPA- B and CD28RE sites. CD28RE contains a 9-base pair consensus sequence and binds optimally to p65 and c-Rel homodimers. Consensus B DNA sequences are underlined. The two B DNA half-sites are indicated by positive and negative numbering with the position 0 corresponding to a central nucleotide base pair that passes through the pseudodyad axis of the protein·DNA complex.

Figure 2.
Fig. 2. The structure of the IFN - B·p50·p65 heterodimer complex. a, the two complexes in the asymmetric unit. The p50 and p65 subunits are shown in yellow and green, respectively. The DNA strands are shown as orange and cyan spheres. b, the crystallographic contacts between complex 1 and a symmetrical complex. c, the entire complex is viewed down the DNA axis. p50 and p65 subunits are indicated by yellow and green, respectively. d, the detailed interactions across the subunit interface centered around Tyr-267 of p50 and Phe-213 of p65.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 24694-24700) copyright 2002.

Figures were selected by the author.