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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7450 | |||||||||
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Title | Cryo-EM structure of the Gasdermin A3 membrane pore | |||||||||
![]() | Gasdermin A3 pore with 28-fold symmetry | |||||||||
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Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
![]() | Ruan J / Xia S / Wu H | |||||||||
![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.4 KB 13.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.5 KB | Display | ![]() |
Images | ![]() | 82.5 KB | ||
Others | ![]() ![]() | 108.6 MB 108.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 78.1 KB | Display | ![]() |
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Full document | ![]() | 77.2 KB | Display | |
Data in XML | ![]() | 492 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Gasdermin A3 pore with 28-fold symmetry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Half map 1 of the Gasdermin A3 pore with 28-fold symmetry
File | emd_7450_half_map_1.map | ||||||||||||
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Annotation | Half map 1 of the Gasdermin A3 pore with 28-fold symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2 of the Gasdermin A3 pore with 28-fold symmetry
File | emd_7450_half_map_2.map | ||||||||||||
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Annotation | Half map 2 of the Gasdermin A3 pore with 28-fold symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Gasdermin A3 N-terminal domain
Entire | Name: Gasdermin A3 N-terminal domain |
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Components |
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-Supramolecule #1: Gasdermin A3 N-terminal domain
Supramolecule | Name: Gasdermin A3 N-terminal domain / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: mouse Gasdermin A3 pores with 28-fold symmetry |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Experimental: 810 KDa |
-Macromolecule #1: Gasdermin A3
Macromolecule | Name: Gasdermin A3 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHMPVFEDVT RALVRELNPR GDLTPLDSLI DFKHFRPFCL VLRKRKSTLF WGARYVRTDY TLLDLLEPGS SPSDLTDSGN FSFKNMLDVQ VQGLVEVPKT VKVKGTAGLS QSSTLEVQTL SVAPSALENL KKERKLSADH SFLNEMRYHE KNLYVVMEAV EAKQEVTVEQ ...String: MHMPVFEDVT RALVRELNPR GDLTPLDSLI DFKHFRPFCL VLRKRKSTLF WGARYVRTDY TLLDLLEPGS SPSDLTDSGN FSFKNMLDVQ VQGLVEVPKT VKVKGTAGLS QSSTLEVQTL SVAPSALENL KKERKLSADH SFLNEMRYHE KNLYVVMEAV EAKQEVTVEQ TGNANAIFSL PSLALLGLQG SLNNNKAVTI PKGCVLAYRV RLLRVFLFNL WDIPYICNDS MQTFPKIRRV PCSAFISPTQ MISEEPEEEK LIGELEVLFQ |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |