+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32484 | |||||||||
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Title | Human NLRP1 complexed with thioredoxin | |||||||||
Map data | B-factor sharpened map | |||||||||
Sample |
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Keywords | NLRP1 / inflammasome / thioredoxin / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / The NLRP1 inflammasome / self proteolysis / Hydrolases; Acting on peptide bonds (peptidases) / pattern recognition receptor signaling pathway / pattern recognition receptor activity / cellular response to UV-B ...NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / The NLRP1 inflammasome / self proteolysis / Hydrolases; Acting on peptide bonds (peptidases) / pattern recognition receptor signaling pathway / pattern recognition receptor activity / cellular response to UV-B / pyroptotic inflammatory response / cysteine-type endopeptidase activator activity involved in apoptotic process / response to muramyl dipeptide / antiviral innate immune response / protein-disulfide reductase activity / 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 / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / double-stranded RNA binding / peptidase activity / regulation of inflammatory response / double-stranded DNA binding / regulation of apoptotic process / neuron apoptotic process / defense response to virus / defense response to bacterium / protein domain specific binding / apoptotic process / nucleolus / enzyme binding / signal transduction / ATP hydrolysis activity / nucleoplasm / ATP binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Spodoptera frugiperda (fall armyworm) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Zhang Z / Ohto U | |||||||||
Funding support | 1 items
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Citation | Journal: Nature / Year: 2023 Title: Structural basis for thioredoxin-mediated suppression of NLRP1 inflammasome. Authors: Zhikuan Zhang / Takuma Shibata / Akiko Fujimura / Jiro Kitaura / Kensuke Miyake / Umeharu Ohto / Toshiyuki Shimizu / Abstract: Inflammasome sensors detect pathogen- and danger-associated molecular patterns and promote inflammation and pyroptosis. NLRP1 was the first inflammasome sensor to be described, and its ...Inflammasome sensors detect pathogen- and danger-associated molecular patterns and promote inflammation and pyroptosis. NLRP1 was the first inflammasome sensor to be described, and its hyperactivation is linked to autoinflammatory disease and cancer. However, the mechanism underlying the activation and regulation of NLRP1 has not been clearly elucidated. Here we identify ubiquitously expressed endogenous thioredoxin (TRX) as a binder of NLRP1 and a suppressor of the NLRP1 inflammasome. The cryo-electron microscopy structure of human NLRP1 shows NLRP1 bound to Spodoptera frugiperda TRX. Mutagenesis studies of NLRP1 and human TRX show that TRX in the oxidized form binds to the nucleotide-binding domain subdomain of NLRP1. This observation highlights the crucial role of redox-active cysteines of TRX in NLRP1 binding. Cellular assays reveal that TRX suppresses NLRP1 inflammasome activation and thus negatively regulates NLRP1. Our data identify the TRX system as an intrinsic checkpoint for innate immunity and provide opportunities for future therapeutic intervention in NLRP1 inflammasome activation targeting this system. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32484.map.gz | 2.1 MB | EMDB map data format | |
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Header (meta data) | emd-32484-v30.xml emd-32484.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
Images | emd_32484.png | 77.4 KB | ||
Filedesc metadata | emd-32484.cif.gz | 6.1 KB | ||
Others | emd_32484_additional_1.map.gz emd_32484_additional_2.map.gz | 11.9 MB 13.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32484 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32484 | HTTPS FTP |
-Validation report
Summary document | emd_32484_validation.pdf.gz | 373.9 KB | Display | EMDB validaton report |
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Full document | emd_32484_full_validation.pdf.gz | 373.4 KB | Display | |
Data in XML | emd_32484_validation.xml.gz | 5.3 KB | Display | |
Data in CIF | emd_32484_validation.cif.gz | 5.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32484 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32484 | HTTPS FTP |
-Related structure data
Related structure data | 7wgeMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32484.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | B-factor sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.245 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unsharpened map
File | emd_32484_additional_1.map | ||||||||||||
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Annotation | Unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: DeepEMhancer sharpened map
File | emd_32484_additional_2.map | ||||||||||||
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Annotation | DeepEMhancer sharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : hNLRP1 complexed with sfTRX
Entire | Name: hNLRP1 complexed with sfTRX |
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Components |
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-Supramolecule #1: hNLRP1 complexed with sfTRX
Supramolecule | Name: hNLRP1 complexed with sfTRX / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: hNLRP1
Supramolecule | Name: hNLRP1 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Spodoptera frugiperda (fall armyworm) |
-Supramolecule #3: sfTRX
Supramolecule | Name: sfTRX / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: NACHT, LRR and PYD domains-containing protein 1, N-terminus
Macromolecule | Name: NACHT, LRR and PYD domains-containing protein 1, N-terminus type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 101.999953 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: SFPYSPSEPH LGSPSQPTST AVLMPWIHEL PAGCTQGSER RVLRQLPDTS GRRWREISAS LLYQALPSSP DHESPSQESP NAPTSTAVL GSWGSPPQPS LAPREQEAPG TQWPLDETSG IYYTEIRERE REKSEKGRPP WAAVVGTPPQ AHTSLQPHHH P WEPSVRES ...String: SFPYSPSEPH LGSPSQPTST AVLMPWIHEL PAGCTQGSER RVLRQLPDTS GRRWREISAS LLYQALPSSP DHESPSQESP NAPTSTAVL GSWGSPPQPS LAPREQEAPG TQWPLDETSG IYYTEIRERE REKSEKGRPP WAAVVGTPPQ AHTSLQPHHH P WEPSVRES LCSTWPWKNE DFNQKFTQLL LLQRPHPRSQ DPLVKRSWPD YVEENRGHLI EIRDLFGPGL DTQEPRIVIL QG AAGIGKS TLARQVKEAW GRGQLYGDRF QHVFYFSCRE LAQSKVVSLA ELIGKDGTAT PAPIRQILSR PERLLFILDG VDE PGWVLQ EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG FSESSRKEYF YRYF TDERQ AIRAFRLVKS NKELWALCLV PWVSWLACTC LMQQMKRKEK LTLTSKTTTT LCLHYLAQAL QAQPLGPQLR DLCSL AAEG IWQKKTLFSP DDLRKHGLDG AIISTFLKMG ILQEHPIPLS YSFIHLCFQE FFAAMSYVLE DEKGRGKHSN CIIDLE KTL EAYGIHGLFG ASTTRFLLGL LSDEGEREME NIFHCRLSQG RNLMQWVPSL QLLLQPHSLE SLHCLYETRN KTFLTQV MA HFEEMGMCVE TDMELLVCTF CIKFSRHVKK LQLIEGRQHR STWSPTMVVL FRWVPVTDAY WQILFSVLKV TRNLKELD L SGNSLSHSAV KSLCKTLRRP RCLLETLRLA GCGLTAEDCK DLAFGLRANQ TLTELDLSFN VLTDAGAKHL CQRLRQPSC KLQRLQLVSC GLTSDCCQDL ASVLSASPSL KELDLQQNNL DDVGVRLLCE GLRHPACKLI RLGLDQTTLS DEMRQELRAL EQEKPQLLI FSRRKPSVMT P UniProtKB: NACHT, LRR and PYD domains-containing protein 1 |
-Macromolecule #2: Thioredoxin
Macromolecule | Name: Thioredoxin / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Spodoptera frugiperda (fall armyworm) |
Molecular weight | Theoretical: 11.94489 KDa |
Sequence | String: MSIHIKDSDD LKNRLAEAGD KLVVIDFMAT WCGPCKMIGP KLDEMANEMS DCIVVLKVDV DECEDIATEY NINSMPTFVF VKNSKKIEE FSGANVDKLR NTIIKLK UniProtKB: Thioredoxin |
-Macromolecule #3: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER
Macromolecule | Name: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / type: ligand / ID: 3 / Number of copies: 1 / Formula: AGS |
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Molecular weight | Theoretical: 523.247 Da |
Chemical component information | ChemComp-AGS: |
-Macromolecule #4: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 63.2 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE / Details: Ab initio reconstruction |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 72304 |
Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |