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

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^PYD filament formation. To elucidate the molecular basis of AIM2-induced ASC^PYD polymerization, we generated AIM2^PYD 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.

SUBMITTER: Lu A 

PROVIDER: S-EPMC4646227 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature