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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of a bacterial gasdermin double pore assembly | |||||||||
![]() | double-pore map | |||||||||
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![]() | gasdermin / pore-forming protein / pyroptosis / bacteria / 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: 7.3 Å | |||||||||
![]() | Johnson AG / Mayer ML / Kranzusch PJ | |||||||||
Funding support | ![]()
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![]() | ![]() 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 have revealed the ...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 have revealed the functions and architectures of assemblies comprising 24 to 33 protomers, 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 more than 50 protomers. We determine a cryo-electron microscopy structure of a Vitiosangium bGSDM in an active 'slinky'-like oligomeric conformation and analyse 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 | ![]() | 75.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.1 KB 15.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.2 KB | Display | ![]() |
Images | ![]() | 69.1 KB | ||
Masks | ![]() | 149.9 MB | ![]() | |
Filedesc metadata | ![]() | 5 KB | ||
Others | ![]() ![]() | 139.1 MB 139.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 909.6 KB | Display | ![]() |
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Full document | ![]() | 909.2 KB | Display | |
Data in XML | ![]() | 19.7 KB | Display | |
Data in CIF | ![]() | 25.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8sl0C 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
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Annotation | double-pore map | ||||||||||||||||||||
Voxel size | X=Y=Z: 2.66 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: double-pore half map A
File | emd_43511_half_map_1.map | ||||||||||||
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Annotation | double-pore half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: double-pore half map B
File | emd_43511_half_map_2.map | ||||||||||||
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Annotation | double-pore half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Vitiosangium bGSDM in double-pore assembly
Entire | Name: Vitiosangium bGSDM in double-pore assembly |
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Components |
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-Supramolecule #1: Vitiosangium bGSDM in double-pore assembly
Supramolecule | Name: Vitiosangium bGSDM in double-pore assembly / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Vitiosangium bacterial gasdermin
Macromolecule | Name: Vitiosangium bacterial gasdermin / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SGLCSDPAIT YLKRLGYNVV RLPREGIQPL HLLGQQRGTV EYLGSLEKLI TQPPSEPPAI TRDQAAAGIN GQKTENLSFS IGINILKSVL AQFGAGAGIE AQYNQARKVR FEFSNVLADS VEPLAVGQFL KMAEVDADNP VLKQYVLGNG RLYVITQVIK SNEFTVAAEK ...String: SGLCSDPAIT YLKRLGYNVV RLPREGIQPL HLLGQQRGTV EYLGSLEKLI TQPPSEPPAI TRDQAAAGIN GQKTENLSFS IGINILKSVL AQFGAGAGIE AQYNQARKVR FEFSNVLADS VEPLAVGQFL KMAEVDADNP VLKQYVLGNG RLYVITQVIK SNEFTVAAEK SGGGSIQLDV PEIQKVVGGK LKVEASVSSQ STVTYKGEKQ LVFGFKCFEI GVKNGEITLF ASQLVPR UniProtKB: Gasdermin bGSDM |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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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), 50 mM HECAMEG | ||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD | ||||||||||||
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: 33411 / Average electron dose: 53.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |