X-ray crystal structure of IRF-3 and its functional implications

Nat Struct Biol. 2003 Nov;10(11):922-7. doi: 10.1038/nsb1001. Epub 2003 Oct 12.

Abstract

Transcription factor IRF-3 is post-translationally activated by Toll-like receptor (TLR) signaling and has critical roles in the regulation of innate immunity. Here we present the X-ray crystal structure of the C-terminal regulatory domain of IRF-3(175-427) (IRF-3 175C) at a resolution of 2.3 A. IRF-3 175C is structurally similar to the Mad homology domain 2 of the Smad family. Structural and functional analyses reveal phosphorylation-induced IRF-3 dimerization, which generates an extensive acidic pocket responsible for binding with p300/CBP. Although TLR and Smad signaling are evolutionarily independent, our results suggest that IRF-3 originates from Smad and acquires its function downstream of TLR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Humans
  • Interferon Regulatory Factor-3
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Structure, Tertiary
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Transcription Factors
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human

Associated data

  • PDB/1J2F