title: Structural Mechanisms in NLR Inflammasome Assembly and Signaling.
abstract: Inflammasomes are multimeric protein complexes that mediate the activation of inflammatory caspases. One central component of inflammasomes is nucleotide-binding domain (NBD)- and leucine-rich repeat (LRR)-containing proteins (NLRs) that can function as pattern recognition receptors (PRRs). In resting cells, NLR proteins exist in an auto-inhibited, monomeric, and ADP-bound state. Perception of microbial or damage-associated signals results in NLR oligomerization, thus recruiting inflammatory caspases directly or through the adaptor molecule apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). The assembled NLR inflammasomes serve as dedicated machinery to facilitate the activation of the inflammatory caspases. Here, we review current understanding of the structures of NLR inflammasomes with an emphasis on the molecular mechanisms of their assembly and activation. We also discuss implications of the self-propagation model derived from the NAIP-NLRC4 inflammasomes for the activation of other NLR inflammasomes and a potential role of the C-terminal LRR domain in the activation of an NLR protein.
authors.affiliation: Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. zehan.hu@gmail.com.
authors.forename: Zehan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. chaijj@tsinghua.edu.cn.
authors.forename: Jijie
authors.initials: J
authors.lastname: Chai
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D005810:Multigene Family; D051192:Receptors, Pattern Recognition / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D053468:CARD Signaling Adaptor Proteins; D058847:Inflammasomes; D051192:Receptors, Pattern Recognition
keywords: Assembly and signaling; Inflammasomes; NOD-like receptors; Structural mechanisms