Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2

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Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2

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Title: Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2
Author: Lu, Alvin; Li, Yang; Yin, Qian; Ruan, Jianbin; Yu, Xiong; Egelman, Edward; Wu, Hao

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Citation: Lu, Alvin, Yang Li, Qian Yin, Jianbin Ruan, Xiong Yu, Edward Egelman, and Hao Wu. 2015. “Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.” Cell discovery 1 (1): 15013. doi:10.1038/celldisc.2015.13. http://dx.doi.org/10.1038/celldisc.2015.13.
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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 ASCPYD filament formation. To elucidate the molecular basis of AIM2-induced ASCPYD polymerization, we generated AIM2PYD 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-AIM2PYD filament is a 1-start helix with helical parameters distinct from those of the 3-start ASCPYD filament. However, despite the apparent symmetry difference, helical net and detailed interface analyses reveal minimal changes in subunit packing. GFP-AIM2PYD nucleated ASCPYD filament formation in comparable efficiency as untagged AIM2PYD, suggesting assembly plasticity in both AIM2PYD and ASCPYD. The DNA-binding domain of AIM2 is able to form AIM2/DNA filaments, within which the AIM2PYD is brought into proximity to template ASCPYD 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.
Published Version: doi:10.1038/celldisc.2015.13
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646227/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845293
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