PDBsum entry 2irf

Gene regulation/DNA

PDB id: 2irf

Contents

Protein chains

(+ 0 more) 109 a.a. *

DNA/RNA

Metals

__K ×6

Waters ×397

* Residue conservation analysis

PDB id:

2irf

Name:

Gene regulation/DNA

Title:

Crystal structure of an irf-2/DNA complex.

Structure:

DNA (5'-d(p Ap Ap Gp Tp Gp Ap Ap Ap Gp (5Iu)p Gp A)-3'). Chain: a, b, c. Engineered: yes. DNA (5'-d( Tp Tp Cp Ap Cp Tp Tp Tp Cp Ap Cp (5Iu)p T)-3'). Chain: d, e, f. Engineered: yes. Interferon regulatory factor 2. Chain: g, h, i, j, k, l. Fragment: DNA-binding domain.

Source:

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

Biol. unit:

Dodecamer (from PQS)

Resolution:

2.20Å R-factor: 0.202 R-free: 0.243

Authors:

Y.Fujii,T.Shimizu,M.Kusumoto,Y.Kyogoku,T.Taniguchi,T.Hakoshima

Key ref:

Y.Fujii et al. (1999). Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. EMBO J, 18, 5028-5041. PubMed id: 10487755 DOI: 10.1093/emboj/18.18.5028

Date:

30-May-99 Release date: 08-Oct-99

Protein chains

P23906  (IRF2_MOUSE) -  Interferon regulatory factor 2 from Mus musculus

Seq: 349 a.a.

Struc: 109 a.a.

DNA/RNA chains

A-A-G-T-G-A-A-A-G-5IU-G-A 12 bases

A-A-G-T-G-A-A-A-G-5IU-G-A 12 bases

A-A-G-T-G-A-A-A-G-5IU-G-A 12 bases

T-T-C-A-C-T-T-T-C-A-C-5IU-T 13 bases

T-C-A-C-T-T-T-C-A-C-5IU-T 12 bases

T-T-C-A-C-T-T-T-C-A-C-5IU-T 13 bases

DOI no: 10.1093/emboj/18.18.5028

EMBO J 18:5028-5041 (1999)

PubMed id: 10487755

Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences.

Y.Fujii, T.Shimizu, M.Kusumoto, Y.Kyogoku, T.Taniguchi, T.Hakoshima.

ABSTRACT

There has been growing interest in the role of the IRF (interferon regulatory factor) family of transcription factors in the regulation of immune responses, cytokine signaling, and oncogenesis. These members are characterized by their well-conserved DNA binding domains at the N-terminal regions. Here we report the 2.2 A resolution crystal structure of the DNA binding domain of one such family member, IRF-2, bound to DNA. The structure reveals its recognition sequence, AANNGAAA (here, recognized bases are underlined and in bold, and N indicates any base), and its cooperative binding to a tandem repeat of the GAAA core sequence induced by DNA structure distortions. These facts explain well the diverse binding properties of the IRF family members, which bind to both single and tandemly repeated sequences. Furthermore, we also identified the 'helix-hairpin-strand motif' at the C terminus of the recognition helix as a metal binding site that is commonly found in certain classes of DNA-interactive proteins. Our results provide new insights into the structure and function of this family of transcription factors.

Selected figure(s)

Figure 6.
Figure 6 Model for PU.1 and IRF-4 bound to DNA. A side view of surface representation showing the model for DNA binding domains of PU.1 (green) and IRF-4 (purple) bound to DNA (light green) containing the GGAANNGAAA motif in the B site of the enhancer of the immunoglobulin light chain gene.

Figure 7.
Figure 7 Possible synergistic bindings at enhancer elements. (A) A side view of the surface representation of the IFN- enhancer with the DNA binding domains of the transcription factors; IRFs (purple and wine red) bound to the PRD III and I sites, ATF-2 -c-Jun (blue and green) bound to the PRD IV, and NF- B, p65 (light green) -p50 (light blue) heterodimer bound to the PRD I sites. The DNA sequence and the binding sites are indicated at the top. Minor grooves of the HMG I(Y) binding sites are indicated with labels. The N and C termini are indicated to show the locations of their activation domains that link to the N termini of ATF-2 -Jun and the C termini of IRF and p65. (B) A side view of the surface representation showing the IRF-2 DNA binding domains (purple and wine red) bound to the TATA-box region of the VCAM-1 gene, together with bound TBP (light blue) and the TFIIB core (green). An IRF-2 DNA binding domain (purple) bound to the upstream GAAA core sequence contacts with the N-terminal domain of the TFIIB core.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 5028-5041) copyright 1999.

Figures were selected by an automated process.