Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC

Seamus R. Morrone, Mariusz Matyszewski, Xiong Yu, Michael Delannoy, Edward H. Egelman, Jungsan Sohn

Research output: Contribution to journalArticle

Abstract

AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous supramolecular signalling platform required to launch innate immune responses. We show here that the pyrin domain of AIM2 (AIM2 PYD) drives both filament formation and dsDNA binding. In addition, the dsDNA-binding domain of AIM2 also oligomerizes and assists in filament formation. The ability to oligomerize is critical for binding dsDNA, and in turn permits the size of dsDNA to regulate the assembly of the AIM2 polymers. The AIM2 PYD oligomers define the filamentous structure, and the helical symmetry of the AIM2 PYD filament is consistent with the filament assembled by the PYD of the downstream adaptor ASC. Our results suggest that the role of AIM2 PYD is not autoinhibitory, but generating a structural template by coupling ligand binding and oligomerization is a key signal transduction mechanism in the AIM2 inflammasome.

Original languageEnglish (US)
Article number7827
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 22 2015

Fingerprint

Inflammasomes
Polymerization
filaments
templates
polymerization
assembly
Chemical activation
activation
Signal transduction
Oligomerization
sensors
Sensors
Oligomers
Innate Immunity
Signal Transduction
Polymers
Ligands
oligomers
platforms
ligands

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC. / Morrone, Seamus R.; Matyszewski, Mariusz; Yu, Xiong; Delannoy, Michael; Egelman, Edward H.; Sohn, Jungsan.

In: Nature Communications, Vol. 6, 7827, 22.07.2015.

Research output: Contribution to journalArticle

Morrone, Seamus R. ; Matyszewski, Mariusz ; Yu, Xiong ; Delannoy, Michael ; Egelman, Edward H. ; Sohn, Jungsan. / Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC. In: Nature Communications. 2015 ; Vol. 6.
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