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Open data
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Basic information
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| Title | Structure of Aegerolysin-L pore | |||||||||
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Keywords | Alternaria alternata pore-forming toxin / Aeg-L / TOXIN | |||||||||
| Function / homology | Aeg-L Function and homology information | |||||||||
| Biological species | Alternaria alternata (fungus) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||
Authors | Gao P / Zhao CQ | |||||||||
| Funding support | 1 items
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Citation | Journal: Nature / Year: 2025Title: Epithelial cell membrane perforation induces allergic airway inflammation. Authors: Kejian Shi / Yao Lv / Chunqiu Zhao / Huan Zeng / Yeqiong Wang / Yuxuan Liu / Lin Li / She Chen / Pu Gao / Feng Shao / Mo Xu / ![]() Abstract: Allergens that induce allergic airway inflammation are highly diverse, but they commonly activate type 2 immune responses. Airway epithelial cells are crucial in allergen sensing. However, the shared ...Allergens that induce allergic airway inflammation are highly diverse, but they commonly activate type 2 immune responses. Airway epithelial cells are crucial in allergen sensing. However, the shared features among diverse allergens that elicit similar innate responses, and their epithelial detection mechanisms, remain poorly defined. Here we identify pore-forming proteins as one of the common stimuli of allergic airway inflammation and reveal their immune-activation mechanisms. Using the prevalent mould allergen Alternaria alternata as a model, we established an in vitro system to investigate type 2 innate immune sensing. A six-step biochemical fractionation identified Aeg-S and Aeg-L as the core immune-stimulatory components. Biochemical reconstitution and cryo-electron microscopy reveal that these proteins form 16- to 20-mer transmembrane pore complexes. Their cooperative perforation acts as a bona fide type 2 immune adjuvant to support antigen-specific T helper 2 and immunoglobulin E responses. Genetically engineered A. alternata strains that lack pore-forming activity do not induce allergic responses in mice. Furthermore, pore-forming proteins from various species, despite structural and membrane target differences, are sufficient to trigger respiratory allergies. Perforations in airway epithelial cells initiate allergic responses through two mechanisms: one triggers IL-33 release, and the other involves Ca influx, which activates MAPK signalling and type 2 inflammatory gene expression. These findings provide insight into how type 2 immune responses detect common perturbations caused by structurally diverse stimuli. Targeting downstream signalling of epithelial perforation may open new avenues for treating respiratory allergies. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_64205.map.gz | 632.4 MB | EMDB map data format | |
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| Header (meta data) | emd-64205-v30.xml emd-64205.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
| Images | emd_64205.png | 79.3 KB | ||
| Filedesc metadata | emd-64205.cif.gz | 5.8 KB | ||
| Others | emd_64205_half_map_1.map.gz emd_64205_half_map_2.map.gz | 620.5 MB 620.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-64205 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-64205 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9uj0MC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_64205.map.gz / Format: CCP4 / Size: 669.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #2
| File | emd_64205_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_64205_half_map_2.map | ||||||||||||
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Sample components
-Entire : Aeg-L Pore complex
| Entire | Name: Aeg-L Pore complex |
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| Components |
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-Supramolecule #1: Aeg-L Pore complex
| Supramolecule | Name: Aeg-L Pore complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Alternaria alternata (fungus) |
-Macromolecule #1: Aeg-L
| Macromolecule | Name: Aeg-L / type: protein_or_peptide / ID: 1 Details: Author stated: In the experimental construction, the amino acid sequence bases of the uniprot sequence at positions 204-213 (GASGGGYAVK) were replaced by the 3C restriction site LEVLFQGP. Number of copies: 36 / Enantiomer: LEVO |
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| Source (natural) | Organism: Alternaria alternata (fungus) |
| Molecular weight | Theoretical: 55.44718 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MGEVVPYKAG MQRGQGYNTY LQSLCVKDAV TIERHDDSNP PFKKEYYSEF IEEYEKIAKS MRISAGAAVS GWGQEANVNV DILNRSEFE TSTLTYEVKV LVQHQVSVLD KHSFNKIQTT TPHATYGDRF IADFIKGGHF YARVSITAKN SSETSELKQS A EVAMTMYG ...String: MGEVVPYKAG MQRGQGYNTY LQSLCVKDAV TIERHDDSNP PFKKEYYSEF IEEYEKIAKS MRISAGAAVS GWGQEANVNV DILNRSEFE TSTLTYEVKV LVQHQVSVLD KHSFNKIQTT TPHATYGDRF IADFIKGGHF YARVSITAKN SSETSELKQS A EVAMTMYG VSGKITQEVE RAVSSIKRNA SVKITIIEST GTSKSLEVLF QGPAEESSDL LAVKEKADQF YKDADSGKHS YV LFAVLGK YRNLSNFESY FAPFDYQMAS LRSWALFNDF TLYKAIETMI KAVPESKFKD GPERKTQLIK QAINIFETIR DRV ILISEH PEAAKEDPDH MKPGDFRLEV LNSIQTKLFH AQSQPIPNTD DYWTDVILTT KGSGNQPLFT FPAFDFGDLI GTEV VSFGK KKNGEEYNCL IGERVTSLDD YKELSYFWVF PDSVQKFAME MYGVSKVPTR NYMRVYAADQ SDIENPRPYQ RFWFY VPSA NSPP UniProtKB: Aeg-L, Aeg-L |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS TITAN THEMIS |
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| Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
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Keywords
Alternaria alternata (fungus)
Authors
Citation

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Processing
FIELD EMISSION GUN