Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP

@article{ONeal2005StructuralBF,
  title={Structural Basis for the Activation of Cholera Toxin by Human ARF6-GTP},
  author={Claire J O'Neal and Michael G Jobling and Randall K. Holmes and Wim G. J. Hol},
  journal={Science},
  year={2005},
  volume={309},
  pages={1093 - 1096}
}
The Vibrio cholerae bacterium causes devastating diarrhea when it infects the human intestine. The key event is adenosine diphosphate (ADP)–ribosylation of the human signaling protein GSα, catalyzed by the cholera toxin A1 subunit (CTA1). This reaction is allosterically activated by human ADP-ribosylation factors (ARFs), a family of essential and ubiquitous G proteins. Crystal structures of a CTA1:ARF6-GTP (guanosine triphosphate) complex reveal that binding of the human activator elicits… 
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A Mutational Analysis of Residues in Cholera Toxin A1 Necessary for Interaction with Its Substrate, the Stimulatory G Protein Gsα
TLDR
Variants with single alanine substitutions at surface-exposed residues within these CTA1 motifs were tested for assembly into holotoxin and ADP-ribosylating activity against Gsα and diethylamino-(benzylidineamino)-guanidine (DEABAG), a small substrate predicted to fit into the CTA2 active site.
Crystal structures of pertussis toxin with NAD+ and analogs provide structural insights into the mechanism of its cytosolic ADP-ribosylation activity
Order-disorder-order transitions mediate the activation of cholera toxin.
The Cholera Toxin A13 Subdomain Is Essential for Interaction with ADP-Ribosylation Factor 6 and Full Toxic Activity but Is Not Required for Translocation from the Endoplasmic Reticulum to the Cytosol
TLDR
It is found that the A13 subdomain of CTA1 is important both for interaction with ARF6 and for full expression of enzyme activity in vivo and Surprisingly, however, the A 13 subdomain was not required for ERAD-mediated passage of Cta1 from the ER to the cytosol.
Cholera Toxin Interactions with Host Cell Stress Proteins
TLDR
The intrinsic conformational instability of the CTA1 polypeptide drives host-toxin interactions related to the translocation event and involves both standard and atypical functions for a variety of host chaperones.
Novel bacterial ADP-ribosylating toxins: structure and function
Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this Review, we use prototype bARTTs, such as diphtheria toxin and…
Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens ι-toxin
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The crystal structure of actin-Ia in complex with the nonhydrolyzable NAD analog βTAD suggests a common reaction mechanism for ADPRTs and might be of use in rational drug design to block toxin-substrate recognition.
ADP‐ribosylation factor 6 acts as an allosteric activator for the folded but not disordered cholera toxin A1 polypeptide
TLDR
It is found ARF6 prevents the thermal disordering of structured CTA1 and stimulates the activity of stabilized CTA 1 over a range of temperatures, yet ARF 6 alone did not promote the refolding of disordered CTA2 to an active state.
Contribution of subdomain structure to the thermal stability of the cholera toxin A1 subunit.
TLDR
Observations provide mechanistic insight regarding the thermal unfolding of CTA1, an event which facilitates its subsequent translocation to the cytosol and the disordering of a Cta1 construct lacking the A1(3) subdomain.
The 1.8 Å Cholix Toxin Crystal Structure in Complex with NAD+ and Evidence for a New Kinetic Model
TLDR
This crystal structure of cholix toxin with NAD+ reveals new insights into the reaction mechanism of this bacterial enzyme, and serves as a reference for continuing inhibitor development for this toxin class.
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