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Open data
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Basic information
Entry | Database: PDB / ID: 8ji0 | ||||||
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Title | Cryo-EM structure of the TcsH-CROP in complex with TMPRSS2 | ||||||
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![]() | TOXIN/HYDROLASE / TcsH / TMPESS2 / TOXIN-HYDROLASE complex | ||||||
Function / homology | ![]() transmembrane protease serine 2 / host cell cytosol / detection of maltose stimulus / maltose transport complex / glycosyltransferase activity / carbohydrate transport / protein autoprocessing / carbohydrate transmembrane transporter activity / maltose binding / maltose transport ...transmembrane protease serine 2 / host cell cytosol / detection of maltose stimulus / maltose transport complex / glycosyltransferase activity / carbohydrate transport / protein autoprocessing / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / Attachment and Entry / cysteine-type peptidase activity / serine-type peptidase activity / ATP-binding cassette (ABC) transporter complex / host cell endosome membrane / cell chemotaxis / toxin activity / outer membrane-bounded periplasmic space / viral translation / Induction of Cell-Cell Fusion / periplasmic space / Attachment and Entry / positive regulation of viral entry into host cell / serine-type endopeptidase activity / lipid binding / DNA damage response / host cell plasma membrane / proteolysis / extracellular exosome / extracellular region / nucleoplasm / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
![]() | Zhou, R. / Tao, L. / Zhan, X. | ||||||
Funding support | ![]()
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![]() | ![]() 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 126.6 KB | Display | ![]() |
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PDB format | ![]() | 86.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 27.2 KB | Display | |
Data in CIF | ![]() | 37.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36303MC ![]() 8jhzC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 46712.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O15393, transmembrane protease serine 2 |
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#2: Protein | Mass: 87735.609 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: malE, b4034, JW3994, tcsH / Production host: ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: The TcsH-TMPRSS2 complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 760140 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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