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- EMDB-28583: CryoEM structure of GSDMB pore without transmembrane beta-barrel -
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Open data
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Basic information
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Title | CryoEM structure of GSDMB pore without transmembrane beta-barrel | |||||||||
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Function / homology | ![]() cytotoxic T cell pyroptotic cell death / wide pore channel activity / killing by host of symbiont cells / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
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Method | ![]() ![]() | |||||||||
![]() | Wang C / Ruan J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for GSDMB pore formation and its targeting by IpaH7.8. Authors: Chengliang Wang / Sonia Shivcharan / Tian Tian / Skylar Wright / Danyang Ma / JengYih Chang / Kunpeng Li / Kangkang Song / Chen Xu / Vijay A Rathinam / Jianbin Ruan / ![]() Abstract: Gasdermins (GSDMs) are pore-forming proteins that play critical roles in host defence through pyroptosis. Among GSDMs, GSDMB is unique owing to its distinct lipid-binding profile and a lack of ...Gasdermins (GSDMs) are pore-forming proteins that play critical roles in host defence through pyroptosis. Among GSDMs, GSDMB is unique owing to its distinct lipid-binding profile and a lack of consensus on its pyroptotic potential. Recently, GSDMB was shown to exhibit direct bactericidal activity through its pore-forming activity. Shigella, an intracellular, human-adapted enteropathogen, evades this GSDMB-mediated host defence by secreting IpaH7.8, a virulence effector that triggers ubiquitination-dependent proteasomal degradation of GSDMB. Here, we report the cryogenic electron microscopy structures of human GSDMB in complex with Shigella IpaH7.8 and the GSDMB pore. The structure of the GSDMB-IpaH7.8 complex identifies a motif of three negatively charged residues in GSDMB as the structural determinant recognized by IpaH7.8. Human, but not mouse, GSDMD contains this conserved motif, explaining the species specificity of IpaH7.8. The GSDMB pore structure shows the alternative splicing-regulated interdomain linker in GSDMB as a regulator of GSDMB pore formation. GSDMB isoforms with a canonical interdomain linker exhibit normal pyroptotic activity whereas other isoforms exhibit attenuated or no pyroptotic activity. Overall, this work sheds light on the molecular mechanisms of Shigella IpaH7.8 recognition and targeting of GSDMs and shows a structural determinant in GSDMB critical for its pyroptotic activity. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.8 KB 14.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.5 KB | Display | ![]() |
Images | ![]() | 59.7 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Others | ![]() ![]() | 59.1 MB 59.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8et1MC ![]() 8efpC ![]() 8et2C 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
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Voxel size | X=Y=Z: 1.66 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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Density Histograms |
-Half map: #1
File | emd_28583_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_28583_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : GSDMB-pore
Entire | Name: GSDMB-pore |
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Components |
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-Supramolecule #1: GSDMB-pore
Supramolecule | Name: GSDMB-pore / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all / Details: C24 symmetry |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Isoform 1 of Gasdermin-B
Macromolecule | Name: Isoform 1 of Gasdermin-B / type: protein_or_peptide / ID: 1 / Number of copies: 24 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 46.84825 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MFSVFEEITR IVVKEMDAGG DMIAVRSLVD ADRFRCFHLV GEKRTFFGCR HYTTGLTLMD ILDTDGDKWL DELDSGLQGQ KAEFQILDN VDSTGELIVR LPKEITISGS FQGFHHQKIK ISENRISQQY LATLENRKLK RELPFSFRSI NTRENLYLVT E TLETVKEE ...String: MFSVFEEITR IVVKEMDAGG DMIAVRSLVD ADRFRCFHLV GEKRTFFGCR HYTTGLTLMD ILDTDGDKWL DELDSGLQGQ KAEFQILDN VDSTGELIVR LPKEITISGS FQGFHHQKIK ISENRISQQY LATLENRKLK RELPFSFRSI NTRENLYLVT E TLETVKEE TLKSDRQYKF WSQISQGHLS YKHKGQREVT IPPNRVLSYR VKQLVFPNKE TMSAGLDIHF RGKTKSFPEG KS LGSEDSR NMKEKLEDME SVLKDLTEEK RKDVLNSLAK CLGKEDIRQD LEQRVSEVLI SGELHMEDPD KPLLSSLFNA AGV LVEARA KAILDFLDAL LELSEEQQFV AEALEKGTLP LLKDQVKSVM EQNWDELASS PPDMDYDPEA RILCALYVVV SILL ELAEG PTSVSS |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 0.5 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2.0 nm / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: DIFFRACTION![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |