Structure and mechanism of action of botulinum and tetanus neurotoxins: A review

Abstract

Botulinum neurotoxins and tetanus neurotoxins are the strongest known toxins that cause neuroparalytic syndromes in botulism and tetanus. This review aimed to systematize scientific data on the structures and mechanism of actions of botulinum and tetanus neurotoxins. Botulinum and tetanus neurotoxins are proteins containing functional domains responsible for receptor binding, transmembrane translocation, and proteolytic cleavage of proteins required for exocytosis of synaptic vesicles and release of neurotransmitters into the synaptic cleft. The main stages of the botulinum neurotoxins and tetanus neurotoxin action include binding to the presynaptic membrane, internalization of bound toxin into the cytosol via endocytosis, translocation of the L-chain into the cytosol via the HN domain, disruption of the interchain disulfide bond with the release of the L-chain to express its catalytic activity (as a metalloprotease) in the cytosol, and selective cleavage of one or more soluble N-ethylmaleimide-sensitive factor attachment receptor complex proteins with subsequent blockade of neurotransmitter release.