[English] 日本語
Yorodumi
- EMDB-32120: Cryo-EM structure of mouse NLRP3 (full-length) dodecamer -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-32120
TitleCryo-EM structure of mouse NLRP3 (full-length) dodecamer
Map datacryo-EM map of mouse NLRP3 dodecamer
Sample
  • Complex: Mouse NLRP3 (full-length) dodecamer
    • Protein or peptide: NACHT, LRR and PYD domains-containing protein 3
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: 1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea
KeywordsNLR / NOD-like receptor / NLRP3 / Inflammasome / IMMUNE SYSTEM
Function / homology
Function and homology information


The NLRP3 inflammasome / positive regulation of T-helper 17 cell differentiation / Metalloprotease DUBs / detection of biotic stimulus / molecular sensor activity / phosphatidylinositol phosphate binding / canonical inflammasome complex / positive regulation of T-helper 2 cell differentiation / positive regulation of T-helper 2 cell cytokine production / acute inflammatory response ...The NLRP3 inflammasome / positive regulation of T-helper 17 cell differentiation / Metalloprotease DUBs / detection of biotic stimulus / molecular sensor activity / phosphatidylinositol phosphate binding / canonical inflammasome complex / positive regulation of T-helper 2 cell differentiation / positive regulation of T-helper 2 cell cytokine production / acute inflammatory response / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of type 2 immune response / NLRP3 inflammasome complex / positive regulation of cytokine production involved in immune response / leukocyte migration involved in inflammatory response / positive regulation of interleukin-13 production / positive regulation of interleukin-5 production / cellular response to peptidoglycan / osmosensory signaling pathway / phosphatidylinositol-4-phosphate binding / negative regulation of non-canonical NF-kappaB signal transduction / pattern recognition receptor signaling pathway / pyroptotic inflammatory response / positive regulation of interleukin-4 production / microtubule organizing center / signaling adaptor activity / positive regulation of interleukin-1 beta production / ADP binding / protein homooligomerization / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / positive regulation of inflammatory response / cellular response to lipopolysaccharide / regulation of inflammatory response / response to ethanol / defense response to virus / DNA-binding transcription factor binding / 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 / nucleus / membrane / cytoplasm / cytosol
Similarity search - Function
NACHT-associated domain / Fish-specific NACHT associated domain / Fish-specific NACHT associated domain / : / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain / NOD2 winged helix domain / DAPIN domain / DAPIN domain profile. ...NACHT-associated domain / Fish-specific NACHT associated domain / Fish-specific NACHT associated domain / : / NACHT, LRR and PYD domains-containing protein, helical domain HD2 / NLRC4 helical domain HD2 / NOD2, winged helix domain / NOD2 winged helix domain / DAPIN domain / DAPIN domain profile. / PAAD/DAPIN/Pyrin domain / NACHT nucleoside triphosphatase / NACHT domain / NACHT-NTPase domain profile. / PAAD/DAPIN/Pyrin domain / Leucine rich repeat, ribonuclease inhibitor type / Leucine Rich repeat / Death-like domain superfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
NACHT, LRR and PYD domains-containing protein 3
Similarity search - Component
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.55 Å
AuthorsOhto U / Shimizu T
Funding support Japan, 4 items
OrganizationGrant numberCountry
Ministry of Education, Culture, Sports, Science and Technology (Japan)19H03164 Japan
Ministry of Education, Culture, Sports, Science and Technology (Japan)20K16274 Japan
Ministry of Education, Culture, Sports, Science and Technology (Japan)20K15730 Japan
Ministry of Education, Culture, Sports, Science and Technology (Japan)19H00976 Japan
CitationJournal: 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
DepositionOct 30, 2021-
Header (metadata) releaseMar 9, 2022-
Map releaseMar 9, 2022-
UpdateNov 20, 2024-
Current statusNov 20, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7vtq
  • Surface level: 0.01
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7vtq
  • Imaged by Jmol
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_32120.png

Downloads & links

-
Map

FileDownload / File: emd_32120.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationcryo-EM map of mouse NLRP3 dodecamer
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.25 Å/pix.
x 240 pix.
= 298.8 Å		1.25 Å/pix.
x 240 pix.
= 298.8 Å		1.25 Å/pix.
x 240 pix.
= 298.8 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.245 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.01 / Movie #1: 0.01
Minimum - Maximum-0.016758071 - 0.047203977
Average (Standard dev.)0.0004643201 (±0.0035844578)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 298.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.2451.2451.245
M x/y/z240240240
origin x/y/z0.0000.0000.000
length x/y/z298.800298.800298.800
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ330330330
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS240240240
D min/max/mean-0.0170.0470.000

-
Supplemental data

-
Sample components

-
Entire : Mouse NLRP3 (full-length) dodecamer

EntireName: Mouse NLRP3 (full-length) dodecamer
Components
  • Complex: Mouse NLRP3 (full-length) dodecamer
    • Protein or peptide: NACHT, LRR and PYD domains-containing protein 3
  • Ligand: ADENOSINE-5'-DIPHOSPHATE
  • Ligand: 1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea

-
Supramolecule #1: Mouse NLRP3 (full-length) dodecamer

SupramoleculeName: Mouse NLRP3 (full-length) dodecamer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Mus musculus (house mouse)

-
Macromolecule #1: NACHT, LRR and PYD domains-containing protein 3

MacromoleculeName: NACHT, LRR and PYD domains-containing protein 3 / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 121.415977 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: HHHHHHDYKD DDDKLEVLFQ GPEFMTSVRC KLAQYLEDLE DVDLKKFKMH LEDYPPEKGC IPVPRGQMEK ADHLDLATLM IDFNGEEKA WAMAVWIFAA INRRDLWEKA KKDQPEWNDT CTSHSSMVCQ EDSLEEEWMG LLGYLSRISI CKKKKDYCKM Y RRHVRSRF ...String:
HHHHHHDYKD DDDKLEVLFQ GPEFMTSVRC KLAQYLEDLE DVDLKKFKMH LEDYPPEKGC IPVPRGQMEK ADHLDLATLM IDFNGEEKA WAMAVWIFAA INRRDLWEKA KKDQPEWNDT CTSHSSMVCQ EDSLEEEWMG LLGYLSRISI CKKKKDYCKM Y RRHVRSRF YSIKDRNARL GESVDLNSRY TQLQLVKEHP SKQEREHELL TIGRTKMRDS PMSSLKLELL FEPEDGHSEP VH TVVFQGA AGIGKTILAR KIMLDWALGK LFKDKFDYLF FIHCREVSLR TPRSLADLIV SCWPDPNPPV CKILRKPSRI LFL MDGFDE LQGAFDEHIG EVCTDWQKAV RGDILLSSLI RKKLLPKASL LITTRPVALE KLQHLLDHPR HVEILGFSEA KRKE YFFKY FSNELQAREA FRLIQENEVL FTMCFIPLVC WIVCTGLKQQ METGKSLAQT SKTTTAVYVF FLSSLLQSRG GIEEH LFSD YLQGLCSLAA DGIWNQKILF EECDLRKHGL QKTDVSAFLR MNVFQKEVDC ERFYSFSHMT FQEFFAAMYY LLEEEA EGE TVRKGPGGCS DLLNRDVKVL LENYGKFEKG YLIFVVRFLF GLVNQERTSY LEKKLSCKIS QQVRLELLKW IEVKAKA KK LQWQPSQLEL FYCLYEMQEE DFVQSAMDHF PKIEINLSTR MDHVVSSFCI KNCHRVKTLS LGFFHNSPKE EEEERRGG R PLDQVQCVFP DTHVACSSRL VNCCLTSSFC RGLFSSLSTN RSLTELDLSD NTLGDPGMRV LCEALQHPGC NIQRLWLGR CGLSHQCCFD ISSVLSSSQK LVELDLSDNA LGDFGIRLLC VGLKHLLCNL QKLWLVSCCL TSACCQDLAL VLSSNHSLTR LYIGENALG DSGVQVLCEK MKDPQCNLQK LGLVNSGLTS ICCSALTSVL KTNQNFTHLY LRSNALGDTG LRLLCEGLLH P DCKLQMLE LDNCSLTSHS CWNLSTILTH NHSLRKLNLG NNDLGDLCVV TLCEVLKQQG CLLQSLQLGE MYLNRETKRA LE ALQEEKP ELTIVFEISW

UniProtKB: NACHT, LRR and PYD domains-containing protein 3

-
Macromolecule #2: ADENOSINE-5'-DIPHOSPHATE

MacromoleculeName: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 12 / Formula: ADP
Molecular weightTheoretical: 427.201 Da
Chemical component information

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

-
Macromolecule #3: 1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrah...

MacromoleculeName: 1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea
type: ligand / ID: 3 / Number of copies: 12 / Formula: 7YN
Molecular weightTheoretical: 402.464 Da
Chemical component information

ChemComp-7YN:
1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 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
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 68.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: D6 (2x6 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 73930
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more