Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization

分类： 生物学 >> 生物物理学 提交时间： 2016-05-12

Zhang, Liman Ruan, Jianbin Tong, Alexander B. Yin, Qian Li, Yang David, Liron Lu, Alvin Wu, Hao Zhang, Liman Ruan, Jianbin Tong, Alexander B. Yin, Qian Li, Yang David, Liron Lu, Alvin Wu, Hao Chen, Shuobing Wu, Jiayi Ouyang, Qi Mao, Youdong

摘要： 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 similar to 90 degrees 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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