2A9K

Crystal structure of the C3bot-NAD-RalA complex reveals a novel type of action of a bacterial exoenzyme


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

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This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.

Pautsch, A.Vogelsgesang, M.Trankle, J.Herrmann, C.Aktories, K.

(2005) EMBO J 24: 3670-3680

  • DOI: https://doi.org/10.1038/sj.emboj.7600813
  • Primary Citation of Related Structures:  
    2A78, 2A9K

  • PubMed Abstract: 

    C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange.


  • Organizational Affiliation

    Structural Research, Department of Integrated Lead Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ras-related protein Ral-A187Homo sapiensMutation(s): 0 
Gene Names: RALARAL
UniProt & NIH Common Fund Data Resources
Find proteins for P11233 (Homo sapiens)
Explore P11233 
Go to UniProtKB:  P11233
PHAROS:  P11233
GTEx:  ENSG00000006451 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11233
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Mono-ADP-ribosyltransferase C3223Clostridium botulinum D phageMutation(s): 0 
Gene Names: C3
EC: 2.4.2
UniProt
Find proteins for P15879 (Clostridium botulinum D phage)
Explore P15879 
Go to UniProtKB:  P15879
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15879
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.225 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 35.26α = 90
b = 113.85β = 106.4
c = 56.31γ = 90
Software Package:
Software NamePurpose
MAR345data collection
XDSdata reduction
MOLREPphasing
REFMACrefinement
XDSdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-10-11
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description