PDBsum entry 1bft

Transcription factor

PDB id: 1bft

Contents

Protein chains

101 a.a. *

Waters ×267

* Residue conservation analysis

PDB id:

1bft

Name:

Transcription factor

Title:

Structure of nf-kb p65 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)

Resolution:

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

Date:

12-Sep-97 Release date: 28-Jan-98

Protein chains

Q04207  (TF65_MOUSE) -  Transcription factor p65 from Mus musculus

Seq: 549 a.a.

Struc: 101 a.a.

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.

ABSTRACT

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.