6B5B

Cryo-EM structure of the NAIP5-NLRC4-flagellin inflammasome

Summary for 6B5B

• Entry DOI: 10.2210/pdb6b5b/pdb
• EMDB information: 7055
• Descriptor: Baculoviral IAP repeat-containing protein 1e, NLR family CARD domain-containing protein 4, Flagellin (3 entities in total)
• Functional Keywords: innate immunity, molecular complex, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 452140.90

Authors

Tenthorey, J.L.,Haloupek, N.,Lopez-Blanco, J.R.,Grob, P.,Adamson, E.,Hartenian, E.,Lind, N.A.,Bourgeois, N.M.,Chacon, P.,Nogales, E.,Vance, R.E. (deposition date: 2017-09-29, release date: 2017-11-15, Last modification date: 2024-03-13)

Primary citation

Tenthorey, J.L.,Haloupek, N.,Lopez-Blanco, J.R.,Grob, P.,Adamson, E.,Hartenian, E.,Lind, N.A.,Bourgeois, N.M.,Chacon, P.,Nogales, E.,Vance, R.E.
The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion.
Science, 358:888-893, 2017

PubMed Abstract: Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo-electron microscopy structure of the assembled ~1.4-megadalton flagellin-NAIP5-NLRC4 inflammasome, revealing how a ligand activates an NLR. Six distinct NAIP5 domains contact multiple conserved regions of flagellin, prying NAIP5 into an open and active conformation. We show that innate immune recognition of multiple ligand surfaces is a generalizable strategy that limits pathogen evolution and immune escape.

PubMed: 29146805
DOI: 10.1126/science.aao1140

Experimental method

ELECTRON MICROSCOPY (5.2 Å)