+Open data
-Basic information
Entry | Database: PDB / ID: 7vtq | |||||||||||||||
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Title | Cryo-EM structure of mouse NLRP3 (full-length) dodecamer | |||||||||||||||
Components | NACHT, LRR and PYD domains-containing protein 3 | |||||||||||||||
Keywords | IMMUNE SYSTEM / NLR / NOD-like receptor / NLRP3 / Inflammasome | |||||||||||||||
Function / homology | Function and homology information The NLRP3 inflammasome / positive regulation of T-helper 17 cell differentiation / molecular sensor activity / detection of biotic stimulus / Metalloprotease DUBs / positive regulation of cytokine production involved in immune response / canonical inflammasome complex / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex ...The NLRP3 inflammasome / positive regulation of T-helper 17 cell differentiation / molecular sensor activity / detection of biotic stimulus / Metalloprotease DUBs / positive regulation of cytokine production involved in immune response / canonical inflammasome complex / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex / acute inflammatory response / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / osmosensory signaling pathway / positive regulation of type 2 immune response / leukocyte migration involved in inflammatory response / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / cellular response to peptidoglycan / pattern recognition receptor signaling pathway / negative regulation of non-canonical NF-kappaB signal transduction / phosphatidylinositol-4-phosphate binding / microtubule organizing center / pyroptotic inflammatory response / positive regulation of interleukin-4 production / negative regulation of acute inflammatory response / signaling adaptor activity / positive regulation of interleukin-1 beta production / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / ADP binding / protein homooligomerization / response to organic cyclic compound / positive regulation of inflammatory response / regulation of inflammatory response / cellular response to lipopolysaccharide / defense response to virus / DNA-binding transcription factor binding / response to ethanol / sequence-specific DNA binding / defense response to Gram-positive bacterium / inflammatory response / Golgi membrane / innate immune response / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / mitochondrion / extracellular region / ATP binding / membrane / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Mus musculus (house mouse) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å | |||||||||||||||
Authors | Ohto, U. / Shimizu, T. | |||||||||||||||
Funding support | Japan, 4items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation. Authors: Umeharu Ohto / Yukie Kamitsukasa / Hanako Ishida / Zhikuan Zhang / Karin Murakami / Chie Hirama / Sakiko Maekawa / Toshiyuki Shimizu / Abstract: SignificanceThe nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) is a pattern recognition receptor that forms an inflammasome. The cryo-electron ...SignificanceThe nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) is a pattern recognition receptor that forms an inflammasome. The cryo-electron microscopy structure of the dodecameric form of full-length NLRP3 bound to the clinically relevant NLRP3-specific inhibitor MCC950 has established the structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation and the mechanism of action of the NLRP3 specific inhibitor. The inactive NLRP3 oligomer represents the NLRP3 resting state, capable of binding to membranes and is likely disrupted for its activation. Visualization of the inhibitor binding mode will enable optimization of the activity of NLRP3 inflammasome inhibitor drugs. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7vtq.cif.gz | 1.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7vtq.ent.gz | 1.4 MB | Display | PDB format |
PDBx/mmJSON format | 7vtq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vtq_validation.pdf.gz | 2.2 MB | Display | wwPDB validaton report |
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Full document | 7vtq_full_validation.pdf.gz | 2.4 MB | Display | |
Data in XML | 7vtq_validation.xml.gz | 246.2 KB | Display | |
Data in CIF | 7vtq_validation.cif.gz | 363.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vt/7vtq ftp://data.pdbj.org/pub/pdb/validation_reports/vt/7vtq | HTTPS FTP |
-Related structure data
Related structure data | 32120MC 7vtpC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 121415.977 Da / Num. of mol.: 12 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: NLRP3, NALP3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8R4B8 #2: Chemical | ChemComp-ADP / #3: Chemical | ChemComp-7YN / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Mouse NLRP3 (full-length) dodecamer / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) / Cell: ExpiSf9 |
Buffer solution | pH: 7.5 Details: 25 mM HEPES-NaOH (pH 7.5), 0.2 M NaCl, 1 mM MgCl2, 0.5 mM TCEP, 1.0 mM ADP, 0.05 mM MCC950 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 68 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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Symmetry | Point symmetry: D6 (2x6 fold dihedral) |
3D reconstruction | Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 73930 / Symmetry type: POINT |