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The Role of Exoproteases in Governing Intraneuronal Metabolism of Botulinum Toxin

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Abstract

Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases.

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Authors and Affiliations

  1. Department of Medicine, Jefferson Medical College, Philadelphia, PA, USA

    Lance L. Simpson, Andrew B. Maksymowych, Hirokazu Kouguchi, Roop S. Bora & Suresh Joshi

  2. Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia, PA, USA

    Lance L. Simpson

  3. Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA, USA

    Garrett DuBois

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  1. Lance L. Simpson
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  2. Andrew B. Maksymowych
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  3. Hirokazu Kouguchi
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  4. Garrett DuBois
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  5. Roop S. Bora
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  6. Suresh Joshi
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Correspondence to Lance L. Simpson.

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Simpson, L.L., Maksymowych, A.B., Kouguchi, H. et al. The Role of Exoproteases in Governing Intraneuronal Metabolism of Botulinum Toxin. Protein J 24, 155–165 (2005). https://doi.org/10.1007/s10930-005-7839-0

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