Structural mechanism of DNA recognition by the p202 HINa domain: insights into the inhibition of Aim2-mediated inflammatory signalling

Acta Crystallogr F Struct Biol Commun. 2014 Jan;70(Pt 1):21-9. doi: 10.1107/S2053230X1303135X. Epub 2013 Dec 24.


The HIN-200 family of proteins play significant roles in inflammation-related processes. Among them, AIM2 (absent in melanoma 2) and IFI16 (γ-interferon-inducible protein 16) recognize double-stranded DNA to initiate inflammatory responses. In contrast, p202, a mouse interferon-inducible protein containing two HIN domains (HINa and HINb), has been reported to inhibit Aim2-mediated inflammatory signalling in mouse. To understand the inhibitory mechanism, the crystal structure of the p202 HINa domain in complex with a 20 bp DNA was determined, in which p202 HINa nonspecifically recognizes both strands of DNA through electrostatic attraction. The p202 HINa domain binds DNA more tightly than does AIM2 HIN, and the DNA-binding mode of p202 HINa is different from that of the AIM2 HIN and IFI16 HINb domains. These results, together with the reported data on p202 HINb, lead to an interaction model for full-length p202 and dsDNA which provides a conceivable mechanism for the negative regulation of Aim2 inflammasome activation by p202.

Keywords: HIN domains; inflammatory response; p202; protein–DNA complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism*
  • DNA-Binding Proteins
  • Humans
  • Inflammasomes / metabolism
  • Inflammation / metabolism*
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction*
  • Structure-Activity Relationship


  • AIM2 protein, human
  • DNA-Binding Proteins
  • Ifi202b protein, mouse
  • Inflammasomes
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • DNA

Associated data

  • PDB/4LNQ