National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
35GM145363
米国
National Science Foundation (NSF, United States)
MCB1845003
米国
引用
ジャーナル: EMBO J / 年: 2025 タイトル: Structural insights into the atypical filament assembly of pyrin domain-containing IFI16. 著者: Archit Garg / Ewa Niedzialkowska / Jeffrey J Zhou / Jasper Moh / Edward H Egelman / Jungsan Sohn / 要旨: In response to various intracellular stress or damage-associated signals, inflammasomes can be activated and trigger a pyroptotic cell death process through the sequential assembly of structurally ...In response to various intracellular stress or damage-associated signals, inflammasomes can be activated and trigger a pyroptotic cell death process through the sequential assembly of structurally compatible and interacting filamentous oligomers involving the pyrin domains (PYD) of important inflammasome components. The PYD-containing interferon-inducible protein 16 (IFI16) has been suggested as a viral DNA sensor that can induce inflammasome formation, but it also has other inflammasome-independent functions, including interferon production. Here, the cryo-EM structure of the filament assembled by the PYD of human IFI16 reveals a helical architecture distinct from inflammasome PYD filaments. In silico interface energy calculations suggest that the helical architecture of the IFI16 filament prevents interactions with inflammasome PYD filaments. Biochemical and cell biology experiments consistently demonstrate that IFI16 does not directly interact with inflammasome pyrin domains. Together, our results provide insights into the structural basis of the inflammasome-independent functions of IFI16, and also show that strict architectural compatibility requirements for interactions contribute to the signal transduction specificity in inflammasome signaling.