PDBsum entry: 1t2k

Transcription/DNA

PDB id: 1t2k

Contents

Protein chains

110 a.a. *

62 a.a. *

61 a.a. *

DNA/RNA

Waters ×8

* Residue conservation analysis

PDB id:

1t2k

Name:

Transcription/DNA

Title:

Structure of the DNA binding domains of irf3, atf-2 and jun bound to DNA

Structure:

31-mer. Chain: e. Engineered: yes. Other_details: interferon-b enhancer. 31-mer. Chain: f. Engineered: yes. Other_details: interferon-b enhancer. Interferon regulatory factor 3.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: irf3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: jun. Gene: atf2, creb2, crebp1.

Biol. unit:

Hexamer (from PQS)

Resolution:

3.00Å R-factor: 0.257 R-free: 0.296

Authors:

D.Panne,T.Maniatis,S.C.Harrison

Key ref:

D.Panne et al. (2004). Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer. EMBO J, 23, 4384-4393. PubMed id: 15510218 DOI: 10.1038/sj.emboj.7600453

Date:

21-Apr-04 Release date: 16-Nov-04

Protein chains

Q14653  (IRF3_HUMAN) -  Interferon regulatory factor 3

Seq: 427 a.a.

Struc: 110 a.a.

Protein chain

P05412  (JUN_HUMAN) -  Transcription factor AP-1

Seq: 331 a.a.

Struc: 62 a.a.*

Protein chain

P15336  (ATF2_HUMAN) -  Cyclic AMP-dependent transcription factor ATF-2

Seq: 505 a.a.

Struc: 61 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: regulatory region DNA binding (5 terms)

DOI no: 10.1038/sj.emboj.7600453

EMBO J 23:4384-4393 (2004)

PubMed id: 15510218

Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.

D.Panne, T.Maniatis, S.C.Harrison.

ABSTRACT

Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN-beta gene. The 3.0 A crystal structure of the DNA-binding domains of ATF-2/c-Jun and two IRF-3 molecules in a complex with 31 base pairs (bp) of the PRDIV-PRDIII region of the IFN-beta enhancer shows that association of the four proteins with DNA creates a continuous surface for the recognition of 24 bp. The structure, together with in vitro binding studies and protein mutagenesis, shows that protein-protein interactions are not critical for cooperative binding. Instead, cooperativity arises mainly through nucleotide sequence-dependent structural changes in the DNA that allow formation of complementary DNA conformations. Because the binding sites overlap on the enhancer, the unit of recognition is the entire nucleotide sequence, not the individual subsites.

Selected figure(s)

Figure 2.
Figure 2 Protein -DNA contacts. Schematic diagram of protein -DNA contacts generated using NUCPLOT (Luscombe et al, 1997). Residues from ATF-2 are in red, c-Jun in blue, IRF-3A in green and IRF-3B in yellow. The core binding sites for each protein are indicated in the corresponding colors. Blue lines indicate hydrogen bonds and red lines van der Waals contacts. Note that contacts by His 40 of IRF-3A and IRF-3B are water mediated.

Figure 6.
Figure 6 Overlapping DNA contacts. Loop L1 of IRF-3A inserts into the minor groove opposite c-Jun, and loop L1 from IRF-3B inserts opposite to helix 3 of IRF-3A.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2004, 23, 4384-4393) copyright 2004.

Figures were selected by the author.