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Botulinum C2 toxin ADP-ribosylates actin.

K Aktories, M Bärmann, I Ohishi

    Nature
    |July 24, 1986
    PubMed
    Summary

    Botulinum C2 toxin, a bacterial toxin, ADP-ribosylates actin, a key cellular protein. This modification significantly impacts actin

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    Area of Science:

    • Biochemistry
    • Cell Biology
    • Toxicology

    Background:

    • Bacterial toxins often utilize ADP-ribosylation to disrupt eukaryotic cell functions.
    • Diphtheria toxin, cholera toxin, and pertussis toxin are known examples affecting protein synthesis and adenylate cyclase regulation.
    • Botulinum C2 toxin, distinct from neurotoxins, exhibits ADP-ribosyltransferase activity and causes various toxic effects.

    Purpose of the Study:

    • To identify the specific protein substrate targeted by Botulinum C2 toxin.
    • To investigate the mechanism and consequences of Botulinum C2 toxin's ADP-ribosylation activity.

    Main Methods:

    • Incubation of intact cells and cell-free preparations with Botulinum C2 toxin.
    • Analysis of protein modification using molecular mass determination.
    • ADP-ribosylation assays using purified actin (G-actin and F-actin) from different sources (liver, skeletal muscle).
    • Viscosity measurements of polymerized actin following toxin treatment.

    Main Results:

    • Botulinum C2 toxin was found to ADP-ribosylate a 43,000 molecular mass protein in cells and cell-free systems.
    • Evidence suggests this 43K protein substrate is actin, undergoing mono-ADP-ribosylation.
    • Purified liver G-actin was efficiently ADP-ribosylated, while liver F-actin and all forms of skeletal muscle actin showed minimal to no modification.
    • ADP-ribosylation of liver G-actin led to a significant decrease in the viscosity of polymerized actin.

    Conclusions:

    • Botulinum C2 toxin specifically targets and ADP-ribosylates actin, primarily in its globular (G) form.
    • This modification of actin by Botulinum C2 toxin alters its polymerization properties, potentially explaining some of the toxin's pathological effects.

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