6Z2G

Crystal structure of human NLRP9 PYD

Summary for 6Z2G

• Entry DOI: 10.2210/pdb6z2g/pdb
• Descriptor: NACHT, LRR and PYD domains-containing protein 9 (2 entities in total)
• Functional Keywords: inflammasome, pyrin domain, pyd, nlrp9, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 11978.97

Authors

Marleaux, M.,Anand, K.,Geyer, M. (deposition date: 2020-05-15, release date: 2020-06-10, Last modification date: 2024-01-24)

Primary citation

Marleaux, M.,Anand, K.,Latz, E.,Geyer, M.
Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly.
Febs Lett., 594:2383-2395, 2020

PubMed Abstract: 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 NLRP9 is not able to self-polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament-forming PYDs revealed that NLRP9 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.

PubMed: 32542665
DOI: 10.1002/1873-3468.13865

Experimental method

X-RAY DIFFRACTION (1.95 Å)