3JBL

Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization

Summary for 3JBL

• Entry DOI: 10.2210/pdb3jbl/pdb
• EMDB information: 6458 6459 6460
• Descriptor: NLR family CARD domain-containing protein 4 (1 entity in total)
• Functional Keywords: inflammasome, nlrc4, naip2, immune system
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 11
• Total formula weight: 1168636.82

Authors

Zhang, L.,Chen, S.,Ruan, J.,Wu, J.,Tong, A.B.,Yin, Q.,Li, Y.,David, L.,Lu, A.,Wang, W.L.,Marks, C.,Ouyang, Q.,Zhang, X.,Mao, Y.,Wu, H. (deposition date: 2015-09-05, release date: 2015-10-21, Last modification date: 2024-11-20)

Primary citation

Zhang, L.,Chen, S.,Ruan, J.,Wu, J.,Tong, A.B.,Yin, Q.,Li, Y.,David, L.,Lu, A.,Wang, W.L.,Marks, C.,Ouyang, Q.,Zhang, X.,Mao, Y.,Wu, H.
Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization.
Science, 350:404-409, 2015

PubMed Abstract: The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90° hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.

PubMed: 26449474
DOI: 10.1126/science.aac5789

Experimental method

ELECTRON MICROSCOPY (4.7 Å)