title: The hierarchical structural architecture of inflammasomes, supramolecular inflammatory machines.
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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, United States.
authors.forename: Arthur V
authors.initials: AV
authors.lastname: Hauenstein
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, United States.
authors.forename: Liman
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, United States. Electronic address: hao.wu@childrens.harvard.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000737:chemistry* / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes