Open AccessCryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization
Author(s) -
Liman Zhang,
Shuobing Chen,
Jianbin Ruan,
Jiayi Wu,
Alex Tong,
Qian Yin,
Yang Li,
Liron David,
Alvin Lu,
Wei Li Wang,
Carolyn Marks,
Qi Ouyang,
Xinzheng Zhang,
Youdong Mao,
Hao Wu
Publication year - 2015
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aac5789
Subject(s) - nlrc4 , inflammasome , microbiology and biotechnology , aim2 , innate immune system , polymerization , biology , protein subunit , biophysics , signal transducing adaptor protein , chemistry , signal transduction , biochemistry , receptor , caspase 1 , organic chemistry , polymer , gene
The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90° hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.
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