Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Immunity (Cambridge, Mass.) Jg. 36; H. 4; S. 561
Hauptverfasser: Jin, Tengchuan, Perry, Andrew, Jiang, Jiansheng, Smith, Patrick, Curry, James A, Unterholzner, Leonie, Jiang, Zhaozhao, Horvath, Gabor, Rathinam, Vijay A, Johnstone, Ricky W, Hornung, Veit, Latz, Eicke, Bowie, Andrew G, Fitzgerald, Katherine A, Xiao, T Sam
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.04.2012
Schlagworte:
Amino Acid Sequence
Cell Line
Crystallography, X-Ray
DNA, B-Form - chemistry
DNA, B-Form - immunology
DNA, B-Form - metabolism
DNA-Binding Proteins - chemistry
Humans
Immunity, Innate
Inflammasomes - genetics
Inflammasomes - metabolism
Models, Molecular
Molecular Sequence Data
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Phosphoproteins - metabolism
Protein Binding
Protein Folding
Protein Structure, Tertiary
Signal Transduction
ISSN:1097-4180, 1097-4180
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2012.02.014