NAIP2-NLRC4 inflammasome
(3JBL)
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I. Introduction
From PubMed: 26449474 DOI: 10.1126/science.aac5789 PubMed 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.
For more information see
Biochemistry
Online: Chapter 2C - Understanding Protein Conformation
II. General Structure
The normal complex has 10 NLRC4 subunits and 1 NAIP2 (which binds the ligand. However, this model has 11 NLRC4 subunits instead (chains A-K).
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