9MUF

Cryo-EM structure of the IFI16-PYD filament

Summary for 9MUF

• Entry DOI: 10.2210/pdb9muf/pdb
• EMDB information: 48631
• Descriptor: Gamma-interferon-inducible protein 16 (1 entity in total)
• Functional Keywords: innate immune sensor ifi16, pyd filament, death domain superfamily, aim2-like receptors (alrs), cryo-em structure, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 18
• Total formula weight: 221464.24

Authors

Garg, A.,Niedzialkowska, E.,Egelman, E.H.,Sohn, J. (deposition date: 2025-01-13, release date: 2025-11-12, Last modification date: 2025-12-31)

Primary citation

Garg, A.,Niedzialkowska, E.,Zhou, J.J.,Moh, J.,Egelman, E.H.,Sohn, J.
Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.
Embo J., 44:7702-7720, 2025

PubMed Abstract: 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.

PubMed: 41193640
DOI: 10.1038/s44318-025-00626-7

Experimental method

ELECTRON MICROSCOPY (3.3 Å)