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- PDB-7v1n: Structure of the Clade 2 C. difficile TcdB in complex with its re... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7v1n | |||||||||
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Title | Structure of the Clade 2 C. difficile TcdB in complex with its receptor TFPI | |||||||||
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![]() | TOXIN / TcdB4 / TFPI / receptor / complex | |||||||||
Function / homology | ![]() negative regulation of blood coagulation / Extrinsic Pathway of Fibrin Clot Formation / host cell cytosol / Transferases; Glycosyltransferases; Hexosyltransferases / endopeptidase inhibitor activity / cellular response to steroid hormone stimulus / glycosyltransferase activity / side of membrane / cysteine-type peptidase activity / host cell endosome membrane ...negative regulation of blood coagulation / Extrinsic Pathway of Fibrin Clot Formation / host cell cytosol / Transferases; Glycosyltransferases; Hexosyltransferases / endopeptidase inhibitor activity / cellular response to steroid hormone stimulus / glycosyltransferase activity / side of membrane / cysteine-type peptidase activity / host cell endosome membrane / caveola / serine-type endopeptidase inhibitor activity / blood coagulation / toxin activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / lipid binding / host cell plasma membrane / cell surface / endoplasmic reticulum / proteolysis / extracellular space / extracellular region / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Luo, J. / Yang, Q. / Zhang, X. / Zhang, Y. / Wan, L. / Li, Y. / Tao, L. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile. Authors: Jianhua Luo / Qi Yang / Xiaofeng Zhang / Yuanyuan Zhang / Li Wan / Xiechao Zhan / Yao Zhou / Liuqing He / Danyang Li / Dazhi Jin / Ying Zhen / Jing Huang / Yanyan Li / Liang Tao / ![]() Abstract: The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C. difficile, ...The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C. difficile, and clade 2 strains exclusively express two TcdB variants (TcdB2 and TcdB4) that use unknown receptors distinct from the classic TcdB. Here, we performed CRISPR/Cas9 screens for TcdB4 and identified tissue factor pathway inhibitor (TFPI) as its receptor. Using cryo-EM, we determined a complex structure of the full-length TcdB4 with TFPI, defining a common receptor-binding region for TcdB. Residue variations within this region divide major TcdB variants into 2 classes: one recognizes Frizzled (FZD), and the other recognizes TFPI. TFPI is highly expressed in the intestinal glands, and recombinant TFPI protects the colonic epithelium from TcdB2/4. These findings establish TFPI as a colonic crypt receptor for TcdB from clade 2 C. difficile and reveal new mechanisms for CDI pathogenesis. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 427.5 KB | Display | ![]() |
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PDB format | ![]() | 350 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 814.1 KB | Display | ![]() |
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Full document | ![]() | 915 KB | Display | |
Data in XML | ![]() | 74.7 KB | Display | |
Data in CIF | ![]() | 111.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 31628MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 270454.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: isoform B4 / Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9EXR0, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases |
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#2: Protein | Mass: 28681.633 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
Sequence details | These conflicts are isoform B4 sequence. |
-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
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||
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 |
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: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 227825 / Symmetry type: POINT |