Light Chain Diversity among the Botulinum Neurotoxins

Toxins
Alexander P Gardner, Joseph T Barbieri

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.

References

Feb 1, 1977·Applied and Environmental Microbiology·B Syuto, S Kubo
Jun 30, 1985·Toxicology and Applied Pharmacology·J A KauffmanL C Sellin
Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·D H HochL L Simpson
Jan 1, 1995·Microbiology and Immunology·K OgumaK Inoue
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·S YamasakiH Niemann
Nov 1, 1995·Quarterly Reviews of Biophysics·C Montecucco, G Schiavo
Mar 14, 1997·Neuroscience Letters·R EleopraD De Grandis
Aug 15, 1997·The Biochemical Journal·G M Cohen
Jan 27, 1998·The Journal of Biological Chemistry·Y ZhangK Ravid
Oct 23, 1998·Nature Structural Biology·D B LacyR C Stevens
Apr 4, 2000·Physiological Reviews·G SchiavoC Montecucco
Oct 12, 2001·Toxicon : Official Journal of the International Society on Toxinology·E A Johnson, M Bradshaw
Feb 20, 2002·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·K R Aoki, B Guyer
Dec 3, 2002·Nature Structural Biology·Lilia K Koriazova, Mauricio Montal
May 1, 1965·Journal of Bacteriology·J GERWINGA KO
May 1, 1994·Trends in Cell Biology·H NiemannR Jahn
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ester Fernández-SalasK Roger Aoki
Apr 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Brent SegelkeBernhard Rupp
Jul 13, 2004·Journal of Applied Microbiology·M D Collins, A K East
Aug 17, 2006·Nature Reviews. Molecular Cell Biology·Reinhard Jahn, Richard H Scheller
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Archana BelleErin K O'Shea
Jan 25, 2007·The Journal of Biological Chemistry·Sheng ChenJoseph T Barbieri
Dec 1, 2007·WormBook : the Online Review of C. Elegans Biology·Edward T Kipreos
Jan 24, 2009·Science·Thomas C Südhof, James E Rothman
Mar 10, 2009·Toxicon : Official Journal of the International Society on Toxinology·Axel T Brunger, Andreas Rummel
May 22, 2009·Journal of Neurochemistry·Thomas Binz, Andreas Rummel
Jun 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sheng Chen, Joseph T Barbieri
Aug 15, 2009·Journal of Cellular Biochemistry·Xuerong ShiRichard K Gordon
Aug 12, 2010·Proceedings of the National Academy of Sciences of the United States of America·John C PriceSina Ghaemmaghami
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yien Che TsaiAllan M Weissman
Jan 12, 2011·FEMS Immunology and Medical Microbiology·Hiroaki ItoToshihiro Watanabe

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Citations

Jun 5, 2019·Expert Opinion on Drug Discovery·Sarah Pirio Richardson, H A Jinnah
Feb 29, 2020·Mini Reviews in Medicinal Chemistry·Miroslav Pohanka
Nov 30, 2019·Toxicon : Official Journal of the International Society on Toxinology·Xiaodan LiRichard A Kammerer
Apr 28, 2021·Expert Opinion on Pharmacotherapy·Marina SvetelVladimir Kostić
Jul 25, 2021·International Journal of Molecular Sciences·Juliette Duchesne de LamotteCamille Nicoleau
Jan 13, 2022·Journal of Proteome Research·Hongmei TangKaishou Xu

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Botulism (ASM)

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

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