6z2g
From Proteopedia
Crystal structure of human NLRP9 PYD
Structural highlights
Function[NLRP9_HUMAN] As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. NLRP9 inflammasome activation may be initiated by DHX9 interaction with viral double-stranded RNA (dsRNA), preferentially to short dsRNA segments.[1] Publication Abstract from PubMedInflammasomes are cytosolic multimeric signaling complexes of the innate immune system that induce activation of caspases. The NOD-like receptor NLRP9 recruits the adaptor protein ASC to form an ASC-dependent inflammasome to limit rotaviral replication in intestinal epithelial cells, but only little is known about the molecular mechanisms regulating and driving its assembly. Here, we present the crystal structure of the human NLRP9 pyrin domain (PYD). We show that NLRP9(PYD) is not able to self-polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament-forming PYDs revealed that NLRP9(PYD) adopts a conformation compatible with filament formation, but several charge inversions of interfacing residues might cause repulsive effects that prohibit self-oligomerization. These results propose that inflammasome assembly of NLRP9 might differ largely from what we know of other inflammasomes. Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly.,Marleaux M, Anand K, Latz E, Geyer M FEBS Lett. 2020 Jun 16. doi: 10.1002/1873-3468.13865. PMID:32542665[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Anand, K | Geyer, M | Marleaux, M | Immune system | Inflammasome | Nlrp9 | Pyd | Pyrin domain
