7POG

High-resolution structure of native toxin A from Clostridioides difficile


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.83 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

High-resolution structure of native toxin A from Clostridioides difficile.

Aminzadeh, A.Larsen, C.E.Boesen, T.Jorgensen, R.

(2022) EMBO Rep 23: e53597-e53597

  • DOI: https://doi.org/10.15252/embr.202153597
  • Primary Citation of Related Structures:  
    7POG

  • PubMed Abstract: 

    Clostridioides difficile infections have emerged as the leading cause of healthcare-associated infectious diarrhea. Disease symptoms are mainly caused by the virulence factors, TcdA and TcdB, which are large homologous multidomain proteins. Here, we report a 2.8 Å resolution cryo-EM structure of native TcdA, unveiling its conformation at neutral pH. The structure uncovers the dynamic movement of the CROPs domain which is induced in response to environmental acidification. Furthermore, the structure reveals detailed information about the interaction area between the CROPs domain and the tip of the delivery and receptor-binding domain, which likely serves to shield the C-terminal part of the hydrophobic pore-forming region from solvent exposure. Similarly, extensive interactions between the globular subdomain and the N-terminal part of the pore-forming region suggest that the globular subdomain shields the upper part of the pore-forming region from exposure to the surrounding solvent. Hence, the TcdA structure provides insights into the mechanism of preventing premature unfolding of the pore-forming region at neutral pH, as well as the pH-induced inter-domain dynamics.


  • Organizational Affiliation

    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Toxin A2,710Clostridioides difficileMutation(s): 0 
UniProt
Find proteins for P16154 (Clostridioides difficile)
Explore P16154 
Go to UniProtKB:  P16154
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16154
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN (Subject of Investigation/LOI)
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 2.83 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Novo Nordisk FoundationDenmarkNNF17OC0029548

Revision History  (Full details and data files)

  • Version 1.0: 2021-12-08
    Type: Initial release
  • Version 1.1: 2022-01-19
    Changes: Database references