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Toxin Structure, Delivery and Action

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Corynebacterium diphtheriae and Related Toxigenic Species

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Abstract

Diphtheria toxin (DTx) consists of a 535 amino acids polypeptide and contains the following three domains: the amino terminal fragment A (FA or catalytic C-domain) that catalyses the transfer of an ADP-ribosyl group of NAD+ to a post-translationally modified histidine (diphthamide) residue on eukaryotic elongation factor 2 (eEF2) and inhibits protein synthesis. Fragment B (FB) consist of the carboxy terminal receptor-binding R-domain, and the translocation (or transmembrane) T-domain. Following binding to its cell surface receptor via R-domain, DTx is internalized through the clathrin-dependent endocytosis. The acid pH created in the early endosomes triggers a conformational change in the toxin leading to the insertion of the T and C-domains in the membrane. The catalytic domain is then translocated into the cytosol across the early endosomal membrane and protein synthesis inhibition occurs. DTx-induced cytotoxicity is versatile, and it includes DNA cleavage and the depolymerisation of actin filaments. FA can interact with both G and F-actin. The binding to the latter appears to take place at the plus end of the filament blocking further polymerisation and it was concluded that G-actin has an inhibitory effect on DTx nuclease activity.

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Authors and Affiliations

  1. Istanbul Faculty of Medicine, Department of Biophysics, Istanbul University, Istanbul, Turkey

    Başak Varol, Bilge Özerman Edis & Muhammet Bektaş

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  1. Başak Varol
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  2. Bilge Özerman Edis
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  3. Muhammet Bektaş
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Correspondence to Muhammet Bektaş .

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  1. Friedrich-Alexander-Universität, Erlangen, Bayern, Germany

    Andreas Burkovski

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Varol, B., Özerman Edis, B., Bektaş, M. (2014). Toxin Structure, Delivery and Action. In: Burkovski, A. (eds) Corynebacterium diphtheriae and Related Toxigenic Species. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7624-1_5

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