6NCV

Cryo-EM structure of NLRP6 PYD filament

Summary for 6NCV

• Entry DOI: 10.2210/pdb6ncv/pdb
• EMDB information: 0438
• Descriptor: NACHT, LRR and PYD domains-containing protein 6 (1 entity in total)
• Functional Keywords: death domain fold, helical assembly, inflammasome, signaling protein, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 21
• Total formula weight: 250563.16

Authors

Shen, C.,Fu, T.M.,Wu, H. (deposition date: 2018-12-12, release date: 2019-01-23, Last modification date: 2024-03-20)

Primary citation

Shen, C.,Lu, A.,Xie, W.J.,Ruan, J.,Negro, R.,Egelman, E.H.,Fu, T.M.,Wu, H.
Molecular mechanism for NLRP6 inflammasome assembly and activation.
Proc. Natl. Acad. Sci. U.S.A., 116:2052-2057, 2019

PubMed Abstract: Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing (NLR) inflammasome family that has been shown to play multiple roles in regulating inflammation and host defenses. Despite the significance of the NLRP6 inflammasome, little is known about the molecular mechanism behind its assembly and activation. Here we present cryo-EM and crystal structures of NLRP6 pyrin domain (PYD). We show that NLRP6 PYD alone is able to self-assemble into filamentous structures accompanied by large conformational changes and can recruit the ASC adaptor using PYD-PYD interactions. Using molecular dynamics simulations, we identify the surface that the NLRP6 PYD filament uses to recruit ASC PYD. We further find that full-length NLRP6 assembles in a concentration-dependent manner into wider filaments with a PYD core surrounded by the NBD and the LRR domain. These findings provide a structural understanding of inflammasome assembly by NLRP6 and other members of the NLR family.

PubMed: 30674671
DOI: 10.1073/pnas.1817221116

Experimental method

ELECTRON MICROSCOPY (3.7 Å)