PDBsum entry 6b5b

Immune system

PDB id: 6b5b

Contents

Protein chains

1199 a.a.

903 a.a.

68 a.a.

PDB id:

6b5b

Name:

Immune system

Title:

Cryo-em structure of the naip5-nlrc4-flagellin inflammasome

Structure:

Baculoviral iap repeat-containing protein 1e. Chain: a. Synonym: neuronal apoptosis inhibitory protein 5. Engineered: yes. Nlr family card domain-containing protein 4. Chain: b, c. Synonym: caspase recruitment domain-containing protein 12, ice protease-activating factor, ipaf. Engineered: yes.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: naip5. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: nlrc4. Legionella pneumophila. Organism_taxid: 446.

Authors:

J.L.Tenthorey,N.Haloupek,J.R.Lopez-Blanco,P.Grob,E.Adamson, E.Hartenian,N.A.Lind,N.M.Bourgeois,P.Chacon,E.Nogales,R.E.Vance

Key ref:

J.L.Tenthorey et al. (2017). The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion. Science, 358, 888-893. PubMed id: 29146805 DOI: 10.1126/science.aao1140

Date:

29-Sep-17 Release date: 15-Nov-17

Protein chain

Q9R016  (BIR1E_MOUSE) -  Baculoviral IAP repeat-containing protein 1e from Mus musculus

Seq: 1403 a.a.

Struc: 1199 a.a.*

Protein chains

Q3UP24  (NLRC4_MOUSE) -  NLR family CARD domain-containing protein 4 from Mus musculus

Seq: 1024 a.a.

Struc: 903 a.a.

Protein chain

Q5ZVV0  (Q5ZVV0_LEGPH) -  Flagellin from Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)

Seq: 475 a.a.

Struc: 68 a.a.*

* PDB and UniProt seqs differ at 33 residue positions (black crosses)

DOI no: 10.1126/science.aao1140

Science 358:888-893 (2017)

PubMed id: 29146805

The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion.

J.L.Tenthorey, N.Haloupek, J.R.López-Blanco, P.Grob, E.Adamson, E.Hartenian, N.A.Lind, N.M.Bourgeois, P.Chacón, E.Nogales, R.E.Vance.

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.