Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor
AU - Jin, Tengchuan
AU - Perry, Andrew
AU - Jiang, Jiansheng
AU - Smith, Patrick
AU - Curry, James A.
AU - Unterholzner, Leonie
AU - Jiang, Zhaozhao
AU - Horvath, Gabor
AU - Rathinam, Vijay A.
AU - Johnstone, Ricky W.
AU - Hornung, Veit
AU - Latz, Eicke
AU - Bowie, Andrew G.
AU - Fitzgerald, Katherine A.
AU - Xiao, T. Sam
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/4/20
Y1 - 2012/4/20
N2 - Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.
AB - Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.
KW - Amino Acid Sequence
KW - Cell Line
KW - Crystallography, X-Ray
KW - DNA, B-Form
KW - DNA-Binding Proteins
KW - Humans
KW - Immunity, Innate
KW - Inflammasomes
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Nuclear Proteins
KW - Phosphoproteins
KW - Protein Binding
KW - Protein Folding
KW - Protein Structure, Tertiary
KW - Signal Transduction
U2 - 10.1016/j.immuni.2012.02.014
DO - 10.1016/j.immuni.2012.02.014
M3 - Journal article
C2 - 22483801
VL - 36
SP - 561
EP - 571
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -