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- EMDB-28087: CryoEM structure of GSDMB in complex with shigella IpaH7.8 -

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Basic information

Entry
Database: EMDB / ID: EMD-28087
TitleCryoEM structure of GSDMB in complex with shigella IpaH7.8
Map dataCryoEM structure of GSDMB in complex with shigella IpaH7.8
Sample
  • Complex: GSDMB-IpaH7.8
    • Complex: E3 ubiquitin-protein ligase ipaH7.8
      • Protein or peptide: Probable E3 ubiquitin-protein ligase ipaH7.8
    • Complex: Gasdermin-B
      • Protein or peptide: Gasdermin-B
KeywordsGSDMB / GSDMD / pyroptosis / ubiquitination / ANTIMICROBIAL PROTEIN / TRANSFERASE-LIPID BINDING PROTEIN complex
Function / homology
Function and homology information


symbiont-mediated suppression of host programmed cell death / cytotoxic T cell pyroptotic cell death / effector-mediated activation of programmed cell death in host / wide pore channel activity / killing by host of symbiont cells / programmed cell death / cardiolipin binding / phosphatidylinositol-4-phosphate binding / pyroptotic inflammatory response / phosphatidylserine binding ...symbiont-mediated suppression of host programmed cell death / cytotoxic T cell pyroptotic cell death / effector-mediated activation of programmed cell death in host / wide pore channel activity / killing by host of symbiont cells / programmed cell death / cardiolipin binding / phosphatidylinositol-4-phosphate binding / pyroptotic inflammatory response / phosphatidylserine binding / phosphatidylinositol-4,5-bisphosphate binding / RING-type E3 ubiquitin transferase / phospholipid binding / ubiquitin protein ligase activity / ubiquitin-dependent protein catabolic process / defense response to Gram-negative bacterium / host cell cytoplasm / killing of cells of another organism / defense response to bacterium / protein ubiquitination / extracellular region / plasma membrane / cytoplasm
Similarity search - Function
Novel E3 ligase domain / C-terminal novel E3 ligase, LRR-interacting / LRR-containing bacterial E3 ligase, N-terminal / Type III secretion system leucine rich repeat protein / : / Gasdermin, PUB domain / Gasdermin PUB domain / Gasdermin, pore forming domain / Gasdermin pore forming domain / Leucine-rich repeats, bacterial type ...Novel E3 ligase domain / C-terminal novel E3 ligase, LRR-interacting / LRR-containing bacterial E3 ligase, N-terminal / Type III secretion system leucine rich repeat protein / : / Gasdermin, PUB domain / Gasdermin PUB domain / Gasdermin, pore forming domain / Gasdermin pore forming domain / Leucine-rich repeats, bacterial type / Leucine-rich repeat profile. / Leucine-rich repeat / Leucine-rich repeat domain superfamily
Similarity search - Domain/homology
E3 ubiquitin-protein ligase ipaH7.8 / Gasdermin-B
Similarity search - Component
Biological speciesShigella flexneri (bacteria) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsWang C / Ruan J
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Nature / Year: 2023
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
DepositionSep 8, 2022-
Header (metadata) releaseMar 29, 2023-
Map releaseMar 29, 2023-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_28087.png

Downloads & links

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Map

FileDownload / File: emd_28087.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryoEM structure of GSDMB in complex with shigella IpaH7.8
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 256 pix.
= 211.968 Å		0.83 Å/pix.
x 256 pix.
= 211.968 Å		0.83 Å/pix.
x 256 pix.
= 211.968 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.828 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.045
Minimum - Maximum-0.09885486 - 0.35181198
Average (Standard dev.)0.00024136387 (±0.009051297)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 211.968 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: CryoEM structure of GSDMB in complex with shigella IpaH7.8

Fileemd_28087_half_map_1.map
AnnotationCryoEM structure of GSDMB in complex with shigella IpaH7.8
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: CryoEM structure of GSDMB in complex with shigella IpaH7.8

Fileemd_28087_half_map_2.map
AnnotationCryoEM structure of GSDMB in complex with shigella IpaH7.8
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : GSDMB-IpaH7.8

EntireName: GSDMB-IpaH7.8
Components
  • Complex: GSDMB-IpaH7.8
    • Complex: E3 ubiquitin-protein ligase ipaH7.8
      • Protein or peptide: Probable E3 ubiquitin-protein ligase ipaH7.8
    • Complex: Gasdermin-B
      • Protein or peptide: Gasdermin-B

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Supramolecule #1: GSDMB-IpaH7.8

SupramoleculeName: GSDMB-IpaH7.8 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: E3 ubiquitin-protein ligase ipaH7.8

SupramoleculeName: E3 ubiquitin-protein ligase ipaH7.8 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Shigella flexneri (bacteria)

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Supramolecule #3: Gasdermin-B

SupramoleculeName: Gasdermin-B / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Probable E3 ubiquitin-protein ligase ipaH7.8

MacromoleculeName: Probable E3 ubiquitin-protein ligase ipaH7.8 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RING-type E3 ubiquitin transferase
Source (natural)Organism: Shigella flexneri (bacteria)
Molecular weightTheoretical: 64.602949 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MFSVNNTHSS VSCSPSINSN STSNEHYLRI LTEWEKNSSP GEERGIAFNR LSQCFQNQEA VLNLSDLNLT SLPELPKHIS ALIVENNKL TSLPKLPAFL KELNADNNRL SVIPELPESL TTLSVRSNQL ENLPVLPNHL TSLFVENNRL YNLPALPEKL K FLHVYYNR ...String:
MFSVNNTHSS VSCSPSINSN STSNEHYLRI LTEWEKNSSP GEERGIAFNR LSQCFQNQEA VLNLSDLNLT SLPELPKHIS ALIVENNKL TSLPKLPAFL KELNADNNRL SVIPELPESL TTLSVRSNQL ENLPVLPNHL TSLFVENNRL YNLPALPEKL K FLHVYYNR LTTLPDLPDK LEILCAQRNN LVTFPQFSDR NNIRQKEYYF HFNQITTLPE SFSQLDSSYR INISGNPLST RV LQSLQRL TSSPDYHGPQ IYFSMSDGQQ NTLHRPLADA VTAWFPENKQ SDVSQIWHAF EHEEHANTFS AFLDRLSDTV SAR NTSGFR EQVAAWLEKL SASAELRQQS FAVAADATES CEDRVALTWN NLRKTLLVHQ ASEGLFDNDT GALLSLGREM FRLE ILEDI ARDKVRTLHF VDEIEVYLAF QTMLAEKLQL STAVKEMRFY GVSGVTANDL RTAEAMVRSR EENEFTDWFS LWGPW HAVL KRTEADRWAQ AEEQKYEMLE NEYSQRVADR LKASGLSGDA DAEREAGAQV MRETEQQIYR QLTDEVLALR LSENGS RLH HS

UniProtKB: E3 ubiquitin-protein ligase ipaH7.8

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Macromolecule #2: Gasdermin-B

MacromoleculeName: Gasdermin-B / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 47.410863 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: 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 TMNIHFRGKT KSFPEEKDGA SS CLGKSLG SEDSRNMKEK LEDMESVLKD LTEEKRKDVL NSLAKCLGKE DIRQDLEQRV SEVLISGELH MEDPDKPLLS SLF NAAGVL VEARAKAILD FLDALLELSE EQQFVAEALE KGTLPLLKDQ VKSVMEQNWD ELASSPPDMD YDPEARILCA LYVV VSILL ELAEGPTSVS S

UniProtKB: Gasdermin-B

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec.
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 66.95 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 113959
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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