[English] 日本語
Yorodumi- PDB-8fw9: Cryo-EM structure of full-length human NLRC4 inflammasome with C1... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8fw9 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of full-length human NLRC4 inflammasome with C12 symmetry | ||||||
Components | NLR family CARD domain-containing protein 4 | ||||||
Keywords | IMMUNE SYSTEM / NLRC4 / NAIP / Inflammasome | ||||||
Function / homology | Function and homology information The IPAF inflammasome / IPAF inflammasome complex / icosanoid biosynthetic process / canonical inflammasome complex / positive regulation of protein processing / caspase binding / activation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response ...The IPAF inflammasome / IPAF inflammasome complex / icosanoid biosynthetic process / canonical inflammasome complex / positive regulation of protein processing / caspase binding / activation of cysteine-type endopeptidase activity / pattern recognition receptor signaling pathway / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / endopeptidase activator activity / detection of bacterium / activation of innate immune response / positive regulation of interleukin-1 beta production / protein homooligomerization / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of NF-kappaB transcription factor activity / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / intracellular membrane-bounded organelle / innate immune response / apoptotic process / magnesium ion binding / protein homodimerization activity / ATP binding / identical protein binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.46 Å | ||||||
Authors | Matico, R.E. / Yu, X. / Miller, R. / Somani, S. / Ricketts, M.D. / Kumar, N. / Steele, R.A. / Medley, Q. / Berger, S. / Faustin, B. / Sharma, S. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural basis of the human NAIP/NLRC4 inflammasome assembly and pathogen sensing. Authors: Rosalie E Matico / Xiaodi Yu / Robyn Miller / Sandeep Somani / M Daniel Ricketts / Nikit Kumar / Ruth A Steele / Quintus Medley / Scott Berger / Benjamin Faustin / Sujata Sharma / Abstract: The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in ...The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in response to cell stress during sterile chronic inflammation. Despite its major role in instigating the subsequent host immune response, a more complete understanding of the molecular events in the formation of the NLRC4 inflammasome in humans is lacking. Here we identify Bacillus thailandensis type III secretion system needle protein (Needle) as a potent trigger of the human NLR family apoptosis inhibitory protein (NAIP)/NLRC4 inflammasome complex formation and determine its structural features by cryogenic electron microscopy. We also provide a detailed understanding of how type III secretion system pathogen components are sensed by human NAIP to form a cascade of NLRC4 protomer through a critical lasso-like motif, a 'lock-key' activation model and large structural rearrangement, ultimately forming the full human NLRC4 inflammasome. These results shed light on key regulatory mechanisms specific to the NLRC4 inflammasome assembly, and the innate immune modalities of pathogen sensing in humans. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8fw9.cif.gz | 544.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8fw9.ent.gz | 438 KB | Display | PDB format |
PDBx/mmJSON format | 8fw9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8fw9_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8fw9_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8fw9_validation.xml.gz | 78.6 KB | Display | |
Data in CIF | 8fw9_validation.cif.gz | 117.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fw/8fw9 ftp://data.pdbj.org/pub/pdb/validation_reports/fw/8fw9 | HTTPS FTP |
-Related structure data
Related structure data | 29498MC 8fvuC 8fw2C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 117027.656 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NLRC4, CARD12, CLAN, CLAN1, IPAF, UNQ6189/PRO20215 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NPP4 |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: the complex of Needle, human NAIP and NLRC4 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
---|---|
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 4.46 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 21406 / Symmetry type: POINT |