6MB2

Cryo-EM structure of the PYD filament of AIM2

Summary for 6MB2

• Entry DOI: 10.2210/pdb6mb2/pdb
• EMDB information: 9064
• Descriptor: Interferon-inducible protein AIM2, Green fluorescent protein (2 entities in total)
• Functional Keywords: filament, higher order, innate immunity, inflammasome, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 30
• Total formula weight: 551462.73

Authors

Lu, A.,Li, Y.,Wu, H. (deposition date: 2018-08-29, release date: 2018-09-05, Last modification date: 2024-10-16)

Primary citation

Lu, A.,Li, Y.,Yin, Q.,Ruan, J.,Yu, X.,Egelman, E.,Wu, H.
Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.
Cell Discov, 1:-, 2015

PubMed Abstract: Absent in melanoma 2 (AIM2) is an essential cytosolic double-stranded DNA receptor that assembles with the adaptor, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 to form the AIM2 inflammasome, which leads to proteolytic maturation of cytokines and pyroptotic cell death. AIM2 contains an N-terminal Pyrin domain (PYD) that interacts with ASC through PYD/PYD interactions and nucleates ASC filament formation. To elucidate the molecular basis of AIM2-induced ASC polymerization, we generated AIM2 filaments fused to green fluorescent protein (GFP) and determined its cryo-electron microscopic (cryo-EM) structure. The map showed distinct definition of helices, allowing fitting of the crystal structure. Surprisingly, the GFP-AIM2 filament is a 1-start helix with helical parameters distinct from those of the 3-start ASC filament. However, despite the apparent symmetry difference, helical net and detailed interface analyses reveal minimal changes in subunit packing. GFP-AIM2 nucleated ASC filament formation in comparable efficiency as untagged AIM2, suggesting assembly plasticity in both AIM2 and ASC. The DNA-binding domain of AIM2 is able to form AIM2/DNA filaments, within which the AIM2 is brought into proximity to template ASC filament assembly. Because ASC is able to interact with many PYD-containing receptors for the formation of inflammasomes, the observed structural plasticity may be critically important for this versatility in the PYD/PYD interactions.

PubMed: 26583071
DOI: 10.1038/celldisc.2015.13

Experimental method

ELECTRON MICROSCOPY (5 Å)