Botulinum neurotoxin type A light chain (BoNT/A-LC)

Botulinum neurotoxin type A light chain (BoNT/A-LC) is the 50 kDa catalytic subunit of the neurotoxin produced by the bacterium Clostridium botulinum (UniProt: P10845). It functions as a highly specific zinc-dependent endopeptidase that targets the Synaptosomal-associated protein 25 (SNAP-25), a key component of the SNARE complex required for vesicle fusion (PubMed: 12503479). Once the toxin is internalized into cholinergic nerve terminals, the light chain is released into the cytosol where it cleaves SNAP-25, thereby blocking the release of the neurotransmitter acetylcholine (StatPearls: NBK557387). This inhibition results in localized flaccid paralysis, which is the basis for both the clinical pathology of botulism and the therapeutic utility of botulinum toxin products (PubChem: CID 11979538). Clinically, BoNT/A-LC is the active moiety in drugs used to treat conditions such as cervical dystonia, chronic migraine, and various cosmetic concerns. Furthermore, the light chain is a primary target for the development of small-molecule inhibitors and antitoxins designed to treat botulinum poisoning (PubMed: 29303570).

Other names

BoNT/A light chainBotulinum toxin type A light chainLC/AZinc metalloprotease BoNT/ASNAP-25 protease

The light chain acts as a zinc-dependent endopeptidase that specifically cleaves the Gln197-Arg198 bond of SNAP-25, preventing the assembly of the SNARE complex and the subsequent release of acetylcholine (PubMed: 12503479).