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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of a bacterial gasdermin slinky-like oligomer | |||||||||
![]() | EM map of Vitiosangium bGSDM slinky oligomer | |||||||||
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![]() | viral mimicry / gasdermin / caspase / autoinhibition / pyroptosis / bats / immunity / cell death / IMMUNE SYSTEM | |||||||||
Function / homology | defense response to virus / plasma membrane / cytoplasm / Gasdermin bGSDM![]() | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Johnson AG / Mayer ML / Kranzusch PJ | |||||||||
Funding support | ![]()
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![]() | Journal: bioRxiv / Year: 2023 Title: Structure and assembly of a bacterial gasdermin pore. Authors: Alex G Johnson / Megan L Mayer / Stefan L Schaefer / Nora K McNamara-Bordewick / Gerhard Hummer / Philip J Kranzusch / ![]() ![]() Abstract: In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis. Studies of human and mouse GSDM pores reveal the functions ...In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis. Studies of human and mouse GSDM pores reveal the functions and architectures of 24-33 protomers assemblies, but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing >50 protomers. We determine a 3.3 Å cryo-EM structure of a bGSDM in an active slinky-like oligomeric conformation and analyze bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, our results support a stepwise model of GSDM pore assembly and suggest that a covalently bound palmitoyl can leave a hydrophobic sheath and insert into the membrane before formation of the membrane-spanning β-strand regions. These results reveal the diversity of GSDM pores found in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 881.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.8 KB 16.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 21.1 KB | Display | ![]() |
Images | ![]() | 46 KB | ||
Filedesc metadata | ![]() | 5.7 KB | ||
Others | ![]() ![]() | 929.2 MB 929.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 938.7 KB | Display | ![]() |
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Full document | ![]() | 938.3 KB | Display | |
Data in XML | ![]() | 31.3 KB | Display | |
Data in CIF | ![]() | 41.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8sl0MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | EM map of Vitiosangium bGSDM slinky oligomer | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.431 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: EM half map A of Vitiosangium bGSDM slinky oligomer
File | emd_40570_half_map_1.map | ||||||||||||
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Annotation | EM half map A of Vitiosangium bGSDM slinky oligomer | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: EM half map B of Vitiosangium bGSDM slinky oligomer
File | emd_40570_half_map_2.map | ||||||||||||
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Annotation | EM half map B of Vitiosangium bGSDM slinky oligomer | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Vitiosangium bGSDM in an active slinky-like oligomeric conformation
Entire | Name: Vitiosangium bGSDM in an active slinky-like oligomeric conformation |
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Components |
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-Supramolecule #1: Vitiosangium bGSDM in an active slinky-like oligomeric conformation
Supramolecule | Name: Vitiosangium bGSDM in an active slinky-like oligomeric conformation type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Gasdermin bGSDM
Macromolecule | Name: Gasdermin bGSDM / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.566246 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SGLCSDPAIT YLKRLGYNVV RLPREGIQPL HLLGQQRGTV EYLGSLEKLI TQPPSEPPAI TRDQAAAGIN GQKTENLSFS IGINILKSV LAQFGAGAGI EAQYNQARKV RFEFSNVLAD SVEPLAVGQF LKMAEVDADN PVLKQYVLGN GRLYVITQVI K SNEFTVAA ...String: SGLCSDPAIT YLKRLGYNVV RLPREGIQPL HLLGQQRGTV EYLGSLEKLI TQPPSEPPAI TRDQAAAGIN GQKTENLSFS IGINILKSV LAQFGAGAGI EAQYNQARKV RFEFSNVLAD SVEPLAVGQF LKMAEVDADN PVLKQYVLGN GRLYVITQVI K SNEFTVAA EKSGGGSIQL DVPEIQKVVG GKLKVEASVS SQSTVTYKGE KQLVFGFKCF EIGVKNGEIT LFASQLVPR UniProtKB: Gasdermin bGSDM |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | filament |
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Sample preparation
Concentration | 1 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
Details: 150 mM NaCl, 20 mM HEPES-HOH (pH 7.5), 5.15 mM DDMAB | ||||||||||||
Grid | Model: Quantifoil / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 2 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 27.0 kPa | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | The sample was monodisperse |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 8156 / Average electron dose: 51.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |