Report

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

See allHide authors and affiliations

Science  08 Oct 2015:
aac5789
DOI: 10.1126/science.aac5789

You are currently viewing the abstract.

View Full Text

Abstract

The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, like the bacterial rod protein PrgJ, and recruit the NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. Here we show that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional ATPase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at a 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.

View Full Text