Abstract
Inflammasomes are caspase-1 activating, molecular inflammatory machines that proteolytically mature pro-inflammatory cytokines and induce pyroptotic cell death during innate immune responses. Recent structural studies of proteins that constitute inflammasomes have yielded fresh insights into their assembly mechanisms. In particular, these include a crystal structure of the CARD-containing NOD-like receptor NLRC4, the crystallographic and electron microscopy (EM) studies of the dsDNA sensors AIM2 and IFI16, and of the regulatory protein p202, and the cryo-EM filament structure of the PYD domain of the inflammasome adapter ASC. These data suggest inflammasome assembly that starts with ligand recognition and release of autoinhibition followed by step-wise rounds of nucleated polymerization from the sensors to the adapters, then to caspase-1. In this elegant manner, inflammasomes form by an 'all-or-none' cooperative mechanism, thereby amplifying the activation of caspase-1. The dense network of filamentous structures predicted by this model has been observed in cells as micron-sized puncta.
🔬 Techniques
🧬 Organisms
✨ Fluorophores
🧪 Sample Preparation
🔬 Cell Lines
💾 Data Repositories
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1
Domain structures of Inflammasome proteins. Domain abbreviations are as follows: PYD: Pyrin domain (yellow and red symbols); HIN: Hematopoietic, Interferon-inducible, Nuclear localization domain (dark...
Figure 2
Structure of monomeric, inactive u0394 CARD mouse NLRC4. (a) The NACHT domain of NLRC4 is divided as follows: NBD: nucleotide-binding domain (cyan); HD1: helical domain 1 (blue); WHD: winged helix dom...
Figure 3
Ligand binding, filament assembly and negative regulation of ALRs. (a) Left: structure of AIM2 PYD (yellow). Middle and right: the HIN/dsDNA complex structure shown respectively in a ribbon diagram an...
Figure 4
ASC PYD filament structure and mechanism of nucleation dependent polymerization in Inflammasome formation. (a) Near atomic resolution cryo-EM structure of a protomer from the ASC PYD filament (PDB ID:...
Figure 5
A schematic diagram for the nucleation dependent polymerization mechanism of AIM2 and NLRP3 inflammasome formation, with proximity-induced autoproteolytic maturation of caspase-1. Proteins and domains...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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