+Open data
-Basic information
Entry | Database: PDB / ID: 7crw | ||||||
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Title | Cryo-EM structure of rNLRP1-rDPP9 complex | ||||||
Components |
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Keywords | IMMUNE SYSTEM | ||||||
Function / homology | Function and homology information negative regulation of cellular defense response / NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / programmed necrotic cell death / positive regulation of pyroptotic inflammatory response / self proteolysis / stress-activated protein kinase signaling cascade / dipeptidyl-peptidase activity ...negative regulation of cellular defense response / NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / programmed necrotic cell death / positive regulation of pyroptotic inflammatory response / self proteolysis / stress-activated protein kinase signaling cascade / dipeptidyl-peptidase activity / Hydrolases; Acting on peptide bonds (peptidases) / pattern recognition receptor activity / cellular response to UV-B / pyroptotic inflammatory response / cell leading edge / response to muramyl dipeptide / antiviral innate immune response / signaling adaptor activity / serine-type peptidase activity / molecular condensate scaffold activity / positive regulation of interleukin-1 beta production / protein homooligomerization / positive regulation of inflammatory response / : / double-stranded RNA binding / peptidase activity / scaffold protein binding / double-stranded DNA binding / regulation of apoptotic process / neuron apoptotic process / microtubule / defense response to virus / defense response to bacterium / protein domain specific binding / neuronal cell body / enzyme binding / ATP hydrolysis activity / protein-containing complex / ATP binding / identical protein binding / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Rattus norvegicus (Norway rat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.18 Å | ||||||
Authors | Huang, M.H. / Zhang, X.X. / Wang, J. / Chai, J.J. | ||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2021 Title: Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Authors: Menghang Huang / Xiaoxiao Zhang / Gee Ann Toh / Qin Gong / Jia Wang / Zhifu Han / Bin Wu / Franklin Zhong / Jijie Chai / Abstract: Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find ...Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND). In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation; however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA-CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA-CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome. | ||||||
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 | 7crw.cif.gz | 408.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7crw.ent.gz | 308 KB | Display | PDB format |
PDBx/mmJSON format | 7crw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7crw_validation.pdf.gz | 767.3 KB | Display | wwPDB validaton report |
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Full document | 7crw_full_validation.pdf.gz | 795 KB | Display | |
Data in XML | 7crw_validation.xml.gz | 57.3 KB | Display | |
Data in CIF | 7crw_validation.cif.gz | 86.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cr/7crw ftp://data.pdbj.org/pub/pdb/validation_reports/cr/7crw | HTTPS FTP |
-Related structure data
Related structure data | 30458MC 7crvC 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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-Components
#1: Protein | Mass: 98203.273 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Dpp9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: M0R781 #2: Protein | Mass: 138577.859 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Nlrp1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: D9I2G3 |
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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: Complex of Nlrp1-FIIND with DPP9 dimer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
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: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.15.1_3469: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.18 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 182116 / Symmetry type: POINT | ||||||||||||||||||||||||
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