ジャーナル: Cell Discov / 年: 2015 タイトル: Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2. 著者: Alvin Lu / Yang Li / Qian Yin / Jianbin Ruan / Xiong Yu / Edward Egelman / Hao Wu / 要旨: 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 ...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.
A: Interferon-inducible protein AIM2 B: Interferon-inducible protein AIM2 C: Interferon-inducible protein AIM2 D: Interferon-inducible protein AIM2 E: Interferon-inducible protein AIM2 F: Interferon-inducible protein AIM2 G: Interferon-inducible protein AIM2 H: Interferon-inducible protein AIM2 I: Interferon-inducible protein AIM2 J: Interferon-inducible protein AIM2 K: Interferon-inducible protein AIM2 L: Interferon-inducible protein AIM2 M: Interferon-inducible protein AIM2 N: Interferon-inducible protein AIM2 O: Interferon-inducible protein AIM2 a: Green fluorescent protein b: Green fluorescent protein c: Green fluorescent protein d: Green fluorescent protein e: Green fluorescent protein f: Green fluorescent protein g: Green fluorescent protein h: Green fluorescent protein i: Green fluorescent protein j: Green fluorescent protein k: Green fluorescent protein l: Green fluorescent protein m: Green fluorescent protein n: Green fluorescent protein o: Green fluorescent protein