Immunity (Cambridge, Mass.), 2012-04, Vol.36 (4), p.561-571
2012
Details
- Autor(en) / Beteiligte
- Titel
- Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor
- Ist Teil von
- Immunity (Cambridge, Mass.), 2012-04, Vol.36 (4), p.561-571
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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. [Display omitted] ► Electrostatic attraction underlies innate dsDNA recognition by the HIN domains ► Both OB folds and the linker between them engage the dsDNA backbone ► An autoinhibited state of AIM2 is activated by DNA that liberates the PYD domain ► DNA serves as an oligomerization platform for the inflammasome assembly
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2012.02.014Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3334467
- Format
- –
- Schlagworte
- Amino Acid Sequence, Autoimmune diseases, Breast cancer, Cell Line, Councils, Crystal structure, Crystallography, X-Ray, Deoxyribonucleic acid, DNA, DNA, B-Form - chemistry, DNA, B-Form - immunology, DNA, B-Form - metabolism, DNA-Binding Proteins - chemistry, Humans, Immune system, Immunity, Innate, Inflammasomes - genetics, Inflammasomes - metabolism, Interferon, interferon-inducible protein, Ligands, Medical research, Melanoma, Models, Molecular, Molecular Sequence Data, Nuclear Proteins - chemistry, Nuclear Proteins - metabolism, Oligomerization, Phosphoproteins - metabolism, Protein Binding, Protein Folding, Protein Structure, Tertiary, Proteins, Pyrin protein, RNA polymerase, Signal Transduction