+Open data
-Basic information
Entry | Database: PDB / ID: 5fna | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM reconstruction of caspase-1 CARD | ||||||
Components | Caspase-1Caspase 1 | ||||||
Keywords | HYDROLASE / CARD / INFLAMMASOME / FILAMENT / SIGNALOSOME / HELICAL RECONSTRUCTION / DEATH DOMAIN | ||||||
Function / homology | Function and homology information caspase-1 / protease inhibitor complex / AIM2 inflammasome complex assembly / The AIM2 inflammasome / AIM2 inflammasome complex / IPAF inflammasome complex / The IPAF inflammasome / NLRP1 inflammasome complex / icosanoid biosynthetic process / cytokine precursor processing ...caspase-1 / protease inhibitor complex / AIM2 inflammasome complex assembly / The AIM2 inflammasome / AIM2 inflammasome complex / IPAF inflammasome complex / The IPAF inflammasome / NLRP1 inflammasome complex / icosanoid biosynthetic process / cytokine precursor processing / canonical inflammasome complex / positive regulation of interleukin-18 production / NLRP3 inflammasome complex / caspase binding / osmosensory signaling pathway / CARD domain binding / positive regulation of tumor necrosis factor-mediated signaling pathway / Interleukin-1 processing / Interleukin-37 signaling / pattern recognition receptor signaling pathway / cellular response to organic substance / signaling receptor ligand precursor processing / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptosis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein autoprocessing / protein maturation / The NLRP3 inflammasome / Pyroptosis / Purinergic signaling in leishmaniasis infection / positive regulation of interleukin-1 beta production / NOD1/2 Signaling Pathway / kinase binding / positive regulation of inflammatory response / cellular response to type II interferon / cellular response to mechanical stimulus / SARS-CoV-1 activates/modulates innate immune responses / regulation of inflammatory response / defense response to virus / regulation of apoptotic process / positive regulation of canonical NF-kappaB signal transduction / endopeptidase activity / cellular response to lipopolysaccharide / microtubule / defense response to bacterium / cysteine-type endopeptidase activity / apoptotic process / nucleolus / signal transduction / protein-containing complex / proteolysis / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4.8 Å | ||||||
Authors | Li, Y. / Lu, A. / Schmidt, F.I. / Yin, Q. / Chen, S. / Fu, T.M. / Tong, A.B. / Ploegh, H.L. / Mao, Y. / Wu, H. | ||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2016 Title: Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism. Authors: Alvin Lu / Yang Li / Florian I Schmidt / Qian Yin / Shuobing Chen / Tian-Min Fu / Alexander B Tong / Hidde L Ploegh / Youdong Mao / Hao Wu / Abstract: Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions ...Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar Ki on caspase-1(CARD) polymerization in vitro and inflammasome activation in cells. Whereas caspase-1(CARD) uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 5fna.cif.gz | 126.7 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5fna.ent.gz | 105.5 KB | Display | PDB format |
PDBx/mmJSON format | 5fna.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fn/5fna ftp://data.pdbj.org/pub/pdb/validation_reports/fn/5fna | HTTPS FTP |
---|
-Related structure data
Related structure data | 3241MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 9590.171 Da / Num. of mol.: 8 / Fragment: CARD DOMAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CASP1, IL1BC, IL1BCE / Plasmid: PDB-HIS-MBP / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P29466, caspase-1 |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: CASPASE-1 CARD / Type: COMPLEX |
---|---|
Buffer solution | Name: 20 MM SODIUM HEPES, 150 MM NACL, 2 MM DTT / pH: 8 / Details: 20 MM SODIUM HEPES, 150 MM NACL, 2 MM DTT |
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: HOLEY CARBON |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Details: LIQUID ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TECNAI ARCTICA / Date: Feb 2, 2015 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Calibrated magnification: 28736 X / Nominal defocus max: 6000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: DIRECT ELECTRON DE-16 (4k x 4k) |
Image scans | Num. digital images: 200 |
-Processing
EM software |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Details: EACH MICROGRAPH | ||||||||||||
3D reconstruction | Method: IHRSR / Resolution: 4.8 Å / Num. of particles: 69222 / Actual pixel size: 0.87 Å Details: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3241. (DEPOSITION ID: 14034). Symmetry type: HELICAL | ||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL / Details: REFINEMENT PROTOCOL--EM | ||||||||||||
Refinement | Highest resolution: 4.8 Å | ||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 4.8 Å
|