Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly

FEBS Letters

article

Michael Marleaux¹  Kanchan Anand¹  Eicke Latz²  Matthias Geyer¹ 

[1] Institute of Structural Biology, University of Bonn;Institute of Innate Immunity, University of Bonn

关键词: ASC specks;    filament;    inflammasomes;    NLRP9;    PYD;    structure;   

DOI  :  10.1002/1873-3468.13865

来源: John Wiley & Sons Ltd.

【 摘 要 】

Inflammasomes 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 NLRP9PYD is not able to self-polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament-forming PYDs revealed that NLRP9PYD 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.

【 授权许可】

Unknown