PDBsum entry: 2pi0

Transcription activator/DNA

PDB id: 2pi0

Contents

Protein chains

98 a.a. *

112 a.a. *

104 a.a. *

DNA/RNA

Waters ×123

* Residue conservation analysis

PDB id:

2pi0

Name:

Transcription activator/DNA

Title:

Crystal structure of irf-3 bound to the prdiii-i regulatory element of the human interferon-b enhancer

Structure:

Interferon regulatory factor 3. Chain: a, b, c, d. Fragment: irf-3 DNA binding domain. Synonym: irf-3. Engineered: yes. Prdiii-i region of human interferon-b promoter strand 1. Chain: e. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: irf3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans. Other_details: this sequence occurs naturally in humans

Resolution:

2.31Å R-factor: 0.185 R-free: 0.264

Authors:

C.R.Escalante,E.Nistal-Villan,S.Leyi,A.Garcia-Sastre, A.K.Aggarwal

Key ref:

C.R.Escalante et al. (2007). Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer. Mol Cell, 26, 703-716. PubMed id: 17560375 DOI: 10.1016/j.molcel.2007.04.022

Date:

12-Apr-07 Release date: 30-Oct-07

Protein chain

Q14653  (IRF3_HUMAN) -  Interferon regulatory factor 3

Seq: 427 a.a.

Struc: 98 a.a.

Protein chains

Q14653  (IRF3_HUMAN) -  Interferon regulatory factor 3

Seq: 427 a.a.

Struc: 112 a.a.

Protein chain

Q14653  (IRF3_HUMAN) -  Interferon regulatory factor 3

Seq: 427 a.a.

Struc: 104 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: regulation of transcription, DNA-dependent (1 term)
• Biochemical function: regulatory region DNA binding (2 terms)

DOI no: 10.1016/j.molcel.2007.04.022

Mol Cell 26:703-716 (2007)

PubMed id: 17560375

Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer.

C.R.Escalante, E.Nistal-Villán, L.Shen, A.García-Sastre, A.K.Aggarwal.

ABSTRACT

Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-beta (IFN-beta) enhanceosome. We present here the structure of IRF-3 DNA binding domain in complex with the complete PRDIII-I regulatory element of the human IFN-beta enhancer. We show that four IRF-3 molecules bind in tandem to, variably spaced, consensus and nonconsensus IRF sites on the composite element. The ability of IRF-3 to bind these variable sites derives in part from two nonconserved arginines (Arg78 and Arg86) that partake in alternate protein-DNA contacts. We also show that the protein-DNA contacts are highly overlapped and that all four IRF sites are required for gene activation in vivo. In addition, we show that changing the nonconsensus IRF sites to consensus sites creates a more efficient enhancer in vivo. Together, the structure and accompanying biological data provide insights into the assembly of the IFN-beta enhanceosome in mammals.

Selected figure(s)

Figure 3.
Figure 3. Protein-DNA Contacts
The contacts are colored according to which IRF-3 DBD makes them: IRF-3A, green; IRF-3B, red; IRF-3C, blue; and IRF-3D, orange. Straight lines correspond to hydrogen bonds, and dotted lines represent van der Waals contacts. Black circles represent water molecules. In the IRF-3A, IRF-3B, IRF-3C, and IRF-3D insets, hydrogen bonds are represented by yellow dotted lines and water molecules are represented as red dots.

Figure 4.
Figure 4. Conformational Variability and Minor Groove Contacts
(A) Minor groove interactions mediated by His40 and Leu42 in IRF-3B. His40 binds to a water molecule (red sphere) that in turn makes hydrogen bonds (yellow dotted lines) with bases. The other IRF-3 DBDs make similar minor groove interactions.
(B) A superposition of the IRF-3A (green), IRF-3B (red), IRF-3C (blue), and IRF-3D (orange) recognition helices to show conformational variability of Arg78, Arg81, and Arg86. Note that arginines that interact with consensus sites (IRF-3B, red; IRF-3D, orange) are closer in conformation than those that interact with the nonconsensus sites (IRF-3A, green; IRF-3C, blue).
(C) Sedimentation velocity analysis showing the g(s^*) distribution of IRF-3 DBDWT/PRDIII-I complex (black) and the mutant IRF3-2Rmut/PRDIII-I complex (red).

The above figures are reprinted by permission from Cell Press: Mol Cell (2007, 26, 703-716) copyright 2007.

Figures were selected by the author.