Paper Publications

Impact Factor:47.0

DOI number:10.1126/science.aac5789

Journal:Science

Place of Publication:USA

Abstract: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.

Indexed by:Journal paper

Discipline:Natural Science

Document Type:J

Volume:350

Page Number:404-409

Translation or Not:no

Date of Publication:2015-10-23

Included Journals:SCI

First Author:Liman Zhang,Shuobing Chen

Correspondence Author:Youdong Mao,Hao Wu

All the Authors:Jianbin Ruan,Jiayi Wu,Alexander B. Tong,Qian Yin,Yang Li,Liron David,Alvin Lu,Wei Li Wang,Carolyn Marks,Qi Ouyang,Xinzheng Zhang