+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7449 | ||||||||||||
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Title | Cryo-EM structure of the Gasdermin A3 membrane pore | ||||||||||||
Map data | Gasdermin A3 membrane pore | ||||||||||||
Sample |
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Keywords | Pyroptosis / Pore forming protein / IMMUNE SYSTEM | ||||||||||||
Function / homology | Function and homology information sebaceous gland cell differentiation / avascular cornea development in camera-type eye / negative regulation of timing of anagen / hair cycle / wide pore channel activity / mammary gland development / positive regulation of extrinsic apoptotic signaling pathway / phosphatidylinositol-4-phosphate binding / skin development / hair follicle morphogenesis ...sebaceous gland cell differentiation / avascular cornea development in camera-type eye / negative regulation of timing of anagen / hair cycle / wide pore channel activity / mammary gland development / positive regulation of extrinsic apoptotic signaling pathway / phosphatidylinositol-4-phosphate binding / skin development / hair follicle morphogenesis / pyroptotic inflammatory response / phosphatidylserine binding / somatic stem cell population maintenance / hair follicle development / extrinsic apoptotic signaling pathway / phosphatidylinositol-4,5-bisphosphate binding / positive regulation of interleukin-1 beta production / mitochondrial membrane / negative regulation of canonical Wnt signaling pathway / defense response to bacterium / positive regulation of apoptotic process / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | ||||||||||||
Authors | Ruan J / Wu H | ||||||||||||
Funding support | United States, 3 items
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Citation | Journal: Nature / Year: 2018 Title: Cryo-EM structure of the gasdermin A3 membrane pore. Authors: Jianbin Ruan / Shiyu Xia / Xing Liu / Judy Lieberman / Hao Wu / Abstract: Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of ...Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of pore formation remains unresolved. Here we present the cryo-electron microscopy structures of the 27-fold and 28-fold single-ring pores formed by the N-terminal fragment of mouse GSDMA3 (GSDMA3-NT) at 3.8 and 4.2 Å resolutions, and of a double-ring pore at 4.6 Å resolution. In the 27-fold pore, a 108-stranded anti-parallel β-barrel is formed by two β-hairpins from each subunit capped by a globular domain. We identify a positively charged helix that interacts with the acidic lipid cardiolipin. GSDMA3-NT undergoes radical conformational changes upon membrane insertion to form long, membrane-spanning β-strands. We also observe an unexpected additional symmetric ring of GSDMA3-NT subunits that does not insert into the membrane in the double-ring pore, which may represent a pre-pore state of GSDMA3-NT. These structures provide a basis that explains the activities of several mutant gasdermins, including defective mutants that are associated with cancer. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7449.map.gz | 16 MB | EMDB map data format | |
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Header (meta data) | emd-7449-v30.xml emd-7449.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_7449_fsc.xml | 13.5 KB | Display | FSC data file |
Images | emd_7449.png | 95.7 KB | ||
Filedesc metadata | emd-7449.cif.gz | 5.2 KB | ||
Others | emd_7449_additional_1.map.gz emd_7449_additional_2.map.gz | 165.4 MB 165.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7449 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7449 | HTTPS FTP |
-Validation report
Summary document | emd_7449_validation.pdf.gz | 411.2 KB | Display | EMDB validaton report |
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Full document | emd_7449_full_validation.pdf.gz | 410.8 KB | Display | |
Data in XML | emd_7449_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | emd_7449_validation.cif.gz | 17.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7449 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7449 | HTTPS FTP |
-Related structure data
Related structure data | 6cb8MC 7450C 7451C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_7449.map.gz / Format: CCP4 / Size: 209.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Gasdermin A3 membrane pore | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Gasdermin A3 membrane pore
File | emd_7449_additional_1.map | ||||||||||||
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Annotation | Gasdermin A3 membrane pore | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Gasdermin A3 membrane pore
File | emd_7449_additional_2.map | ||||||||||||
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Annotation | Gasdermin A3 membrane pore | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Gasdermin A3 N domain
Entire | Name: Gasdermin A3 N domain |
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Components |
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-Supramolecule #1: Gasdermin A3 N domain
Supramolecule | Name: Gasdermin A3 N domain / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 810 KDa |
-Macromolecule #1: Gasdermin-A3
Macromolecule | Name: Gasdermin-A3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 30.401035 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: HMPVFEDVTR ALVRELNPRG DLTPLDSLID FKHFRPFCLV LRKRKSTLFW GARYVRTDYT LLDLLEPGSS PSDLTDSGNF SFKNMLDVQ VQGLVEVPKT VKVKGTAGLS QSSTLEVQTL SVAPSALENL KKERKLSADH SFLNEMRYHE KNLYVVMEAV E AKQEVTVE ...String: HMPVFEDVTR ALVRELNPRG DLTPLDSLID FKHFRPFCLV LRKRKSTLFW GARYVRTDYT LLDLLEPGSS PSDLTDSGNF SFKNMLDVQ VQGLVEVPKT VKVKGTAGLS QSSTLEVQTL SVAPSALENL KKERKLSADH SFLNEMRYHE KNLYVVMEAV E AKQEVTVE QTGNANAIFS LPSLALLGLQ GSLNNNKAVT IPKGCVLAYR VRLLRVFLFN LWDIPYICND SMQTFPKIRR VP CSAFISP TQMISEEPEE EKLIGELEVL FQ UniProtKB: Gasdermin-A3 |
-Macromolecule #2: CARDIOLIPIN
Macromolecule | Name: CARDIOLIPIN / type: ligand / ID: 2 / Number of copies: 1 / Formula: CDL |
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Molecular weight | Theoretical: 1.464043 KDa |
Chemical component information | ChemComp-CDL: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |