Structure and mechanism of action of botulinum and tetanus neurotoxins (literature review)

Abstract

Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the strongest known toxins which cause neuroparalytic syndromes in botulism and tetanus. The purpose of this review was to systematize the scientific data on the structure and mechanism of action of BoNTs and TeNT. It was established that 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 BoNTs and TeNT action are described: 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 release of the L-chain to express its catalytic activity (as a metalloprotease) in the cytosol, and selective cleavage of one or more SNARE complex proteins with subsequent blockade of neurotransmitter release.