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Yorodumi- EMDB-36302: The cryo-EM map of the C-terminal region in the TcsH-TMPRSS2 complex -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36302 | |||||||||
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Title | The cryo-EM map of the C-terminal region in the TcsH-TMPRSS2 complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | TcsH / TMPESS2 / TOXIN/HYDROLASE / TOXIN-HYDROLASE complex | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.0 Å | |||||||||
Authors | Zhou R / Tao L / Zhan X | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin. Authors: Ruoyu Zhou / Liuqing He / Jiahao Zhang / Xiaofeng Zhang / Yanyan Li / Xiechao Zhan / Liang Tao / Abstract: Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane ...Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36302.map.gz | 777.5 MB | EMDB map data format | |
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Header (meta data) | emd-36302-v30.xml emd-36302.xml | 11.6 KB 11.6 KB | Display Display | EMDB header |
Images | emd_36302.png | 23.1 KB | ||
Filedesc metadata | emd-36302.cif.gz | 3.6 KB | ||
Others | emd_36302_half_map_1.map.gz emd_36302_half_map_2.map.gz | 764.4 MB 764.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36302 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36302 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_36302.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_36302_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36302_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : The TcsH-TMPRSS2 complex
Entire | Name: The TcsH-TMPRSS2 complex |
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Components |
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-Supramolecule #1: The TcsH-TMPRSS2 complex
Supramolecule | Name: The TcsH-TMPRSS2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.5 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 6.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 87378 |