+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32119 | |||||||||||||||
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Title | Cryo-EM structure of PYD-deleted human NLRP3 hexamer | |||||||||||||||
Map data | cryo-EM map of PYD-deleted human NLRP3 hexamer | |||||||||||||||
Sample |
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Keywords | NLR / NOD-like receptor / NLRP3 / Inflammasome / IMMUNE SYSTEM | |||||||||||||||
Function / homology | Function and homology information small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / NLRP3 inflammasome complex / positive regulation of type 2 immune response ...small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / NLRP3 inflammasome complex / positive regulation of type 2 immune response / osmosensory signaling pathway / peptidoglycan binding / negative regulation of non-canonical NF-kappaB signal transduction / phosphatidylinositol-4-phosphate binding / pattern recognition receptor signaling pathway / microtubule organizing center / negative regulation of interleukin-1 beta production / positive regulation of interleukin-4 production / pyroptotic inflammatory response / negative regulation of acute inflammatory response / The NLRP3 inflammasome / protein maturation / Purinergic signaling in leishmaniasis infection / signaling adaptor activity / molecular condensate scaffold activity / positive regulation of interleukin-1 beta production / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / protein homooligomerization / Cytoprotection by HMOX1 / cellular response to virus / Metalloprotease DUBs / ADP binding / defense response / negative regulation of inflammatory response / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of NF-kappaB transcription factor activity / protein-macromolecule adaptor activity / cellular response to lipopolysaccharide / DNA-binding transcription factor binding / sequence-specific DNA binding / molecular adaptor activity / inflammatory response / Golgi membrane / innate immune response / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / mitochondrion / extracellular region / ATP binding / identical protein binding / membrane / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.23 Å | |||||||||||||||
Authors | Ohto U / Shimizu T | |||||||||||||||
Funding support | Japan, 4 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_32119.map.gz | 23.3 MB | EMDB map data format | |
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Header (meta data) | emd-32119-v30.xml emd-32119.xml | 11.6 KB 11.6 KB | Display Display | EMDB header |
Images | emd_32119.png | 141.7 KB | ||
Filedesc metadata | emd-32119.cif.gz | 5.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32119 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32119 | HTTPS FTP |
-Related structure data
Related structure data | 7vtpMC 7vtqC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32119.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | cryo-EM map of PYD-deleted human NLRP3 hexamer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.245 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : human NLRP3 (PYD-deleted) hexamer
Entire | Name: human NLRP3 (PYD-deleted) hexamer |
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Components |
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-Supramolecule #1: human NLRP3 (PYD-deleted) hexamer
Supramolecule | Name: human NLRP3 (PYD-deleted) hexamer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: NACHT, LRR and PYD domains-containing protein 3
Macromolecule | Name: NACHT, LRR and PYD domains-containing protein 3 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 106.298539 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: HHHHHHDYKD DDDKLEVLFQ GPEFCKMKKD YRKKYRKYVR SRFQCIEDRN ARLGESVSLN KRYTRLRLIK EHRSQQEREQ ELLAIGKTK TCESPVSPIK MELLFDPDDE HSEPVHTVVF QGAAGIGKTI LARKMMLDWA SGTLYQDRFD YLFYIHCREV S LVTQRSLG ...String: HHHHHHDYKD DDDKLEVLFQ GPEFCKMKKD YRKKYRKYVR SRFQCIEDRN ARLGESVSLN KRYTRLRLIK EHRSQQEREQ ELLAIGKTK TCESPVSPIK MELLFDPDDE HSEPVHTVVF QGAAGIGKTI LARKMMLDWA SGTLYQDRFD YLFYIHCREV S LVTQRSLG DLIMSCCPDP NPPIHKIVRK PSRILFLMDG FDELQGAFDE HIGPLCTDWQ KAERGDILLS SLIRKKLLPE AS LLITTRP VALEKLQHLL DHPRHVEILG FSEAKRKEYF FKYFSDEAQA RAAFSLIQEN EVLFTMCFIP LVCWIVCTGL KQQ MESGKS LAQTSKTTTA VYVFFLSSLL QPRGGSQEHG LCAHLWGLCS LAADGIWNQK ILFEESDLRN HGLQKADVSA FLRM NLFQK EVDCEKFYSF IHMTFQEFFA AMYYLLEEEK EGRTNVPGSR LKLPSRDVTV LLENYGKFEK GYLIFVVRFL FGLVN QERT SYLEKKLSCK ISQQIRLELL KWIEVKAKAK KLQIQPSQLE LFYCLYEMQE EDFVQRAMDY FPKIEINLST RMDHMV SSF CIENCHRVES LSLGFLHNMP KEEEEEEKEG RHLDMVQCVL PSSSHAACSH GLVNSHLTSS FCRGLFSVLS TSQSLTE LD LSDNSLGDPG MRVLCETLQH PGCNIRRLWL GRCGLSHECC FDISLVLSSN QKLVELDLSD NALGDFGIRL LCVGLKHL L CNLKKLWLVS CCLTSACCQD LASVLSTSHS LTRLYVGENA LGDSGVAILC EKAKNPQCNL QKLGLVNSGL TSVCCSALS SVLSTNQNLT HLYLRGNTLG DKGIKLLCEG LLHPDCKLQV LELDNCNLTS HCCWDLSTLL TSSQSLRKLS LGNNDLGDLG VMMFCEVLK QQSCLLQNLG LSEMYFNYET KSALETLQEE KPELTVVFEP SW UniProtKB: NACHT, LRR and PYD domains-containing protein 3 |
-Macromolecule #2: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 6 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Macromolecule #3: 1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrah...
Macromolecule | Name: 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: 6 / Formula: 7YN |
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Molecular weight | Theoretical: 402.464 Da |
Chemical component information | ChemComp-7YN: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | 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 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Applied symmetry - Point group: D3 (2x3 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 105139 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |