7S0Y

Structures of TcdB in complex with Cdc42


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural basis for selective modification of Rho and Ras GTPases by Clostridioides difficile toxin B.

Liu, Z.Zhang, S.Chen, P.Tian, S.Zeng, J.Perry, K.Dong, M.Jin, R.

(2021) Sci Adv 7: eabi4582-eabi4582

  • DOI: https://doi.org/10.1126/sciadv.abi4582
  • Primary Citation of Related Structures:  
    7S0Y, 7S0Z

  • PubMed Abstract: 

    Toxin B (TcdB) is a primary cause of Clostridioides difficile infection (CDI). This toxin acts by glucosylating small GTPases in the Rho/Ras families, but the structural basis for TcdB recognition and selectivity of specific GTPase substrates remain unsolved. Here, we report the cocrystal structures of the glucosyltransferase domain (GTD) of two distinct TcdB variants in complex with human Cdc42 and R-Ras, respectively. These structures reveal a common structural mechanism by which TcdB recognizes Rho and R-Ras. Furthermore, we find selective clustering of adaptive residue changes in GTDs that determine their substrate preferences, which helps partition all known TcdB variants into two groups that display distinct specificities toward Rho or R-Ras. Mutations that selectively disrupt GTPases binding reduce the glucosyltransferase activity of the GTD and the toxicity of TcdB holotoxin. These findings establish the structural basis for TcdB recognition of small GTPases and reveal strategies for therapeutic interventions for CDI.


  • Organizational Affiliation

    Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Toxin B542Clostridioides difficileMutation(s): 0 
Gene Names: tcdBtoxB
EC: 3.4.22
UniProt
Find proteins for P18177 (Clostridioides difficile)
Explore P18177 
Go to UniProtKB:  P18177
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP18177
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division control protein 42 homolog180Homo sapiensMutation(s): 0 
Gene Names: CDC42
EC: 3.6.5.2
UniProt & NIH Common Fund Data Resources
Find proteins for P60953 (Homo sapiens)
Explore P60953 
Go to UniProtKB:  P60953
PHAROS:  P60953
GTEx:  ENSG00000070831 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60953
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GDP (Subject of Investigation/LOI)
Query on GDP

Download Ideal Coordinates CCD File 
N [auth B]GUANOSINE-5'-DIPHOSPHATE
C10 H15 N5 O11 P2
QGWNDRXFNXRZMB-UUOKFMHZSA-N
UDP (Subject of Investigation/LOI)
Query on UDP

Download Ideal Coordinates CCD File 
D [auth A]URIDINE-5'-DIPHOSPHATE
C9 H14 N2 O12 P2
XCCTYIAWTASOJW-XVFCMESISA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
P [auth B],
Q [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
MN (Subject of Investigation/LOI)
Query on MN

Download Ideal Coordinates CCD File 
C [auth A]MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
O [auth B]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.79 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 122.354α = 90
b = 140.948β = 90
c = 111.803γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2021-09-08
    Type: Initial release
  • Version 1.1: 2022-03-23
    Changes: Database references
  • Version 1.2: 2023-10-18
    Changes: Data collection, Refinement description