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Structural basis of cytosolic DNA recognition by innate immune receptors AIM2 and IFI16

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • T Jin
  • A Perry
  • J Jiang
  • JA Curry
  • L Unterholzner
  • Z Jiang
  • G Horvath
  • V Rathinam
  • E Latz
  • KA Fitzgerald
  • AG Bowie
  • TS Xiao


Recognition of DNA by the innate immune system is central to anti-viral and anti-bacteria defenses, as well as a significant contributor to autoimmune diseases involving self DNA. Recently, AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as cytosolic DNA receptors that induce inflammasome formation or interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. The HIN domains form “clamshell” like configurations, the inner surface of which is lined by basic residues enclosing the dsDNA backbone phosphates. The structures define electrostatic attraction as a general principle of non-sequence-specific DNA recognition by the innate receptors, which facilitates DNA-mediated assembly of large signaling complexes such as the inflammasomes. Further binding assay and functional assay have shown that mutations at DNA binding interface impaired direct DNA binding and immune activation.

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