Faculty Collaboration Database

Light Chain Diversity among the Botulinum Neurotoxins. Toxins (Basel) 2018 Jul 02;10(7)

Date

07/14/2018

Pubmed ID

30004421

Pubmed Central ID

PMC6070880

DOI

10.3390/toxins10070268

Scopus ID

2-s2.0-85049650896 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Botulinum neurotoxins (BoNT) are produced by several species of clostridium. There are seven immunologically unique BoNT serotypes (A⁻G). The Centers for Disease Control classifies BoNTs as 'Category A' select agents and are the most lethal protein toxins for humans. Recently, BoNT-like proteins have also been identified in several non-clostridia. BoNTs are di-chain proteins comprised of an N-terminal zinc metalloprotease Light Chain (LC) and a C-terminal Heavy Chain (HC) which includes the translocation and receptor binding domains. The two chains are held together by a disulfide bond. The LC cleaves Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The cleavage of SNAREs inhibits the fusion of synaptic vesicles to the cell membrane and the subsequent release of acetylcholine, which results in flaccid paralysis. The LC controls the catalytic properties and the duration of BoNT action. This review discusses the mechanism for LC catalysis, LC translocation, and the basis for the duration of LC action. Understanding these properties of the LC may expand the applications of BoNT as human therapies.

Author List

Gardner AP, Barbieri JT

Author

Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Botulinum Toxins
Humans
Neurotoxins
SNARE Proteins