Organism of Origin
Botulinum neurotoxin is produced by the bacterium Clostridium botulinum in anaerobic conditions.
Protein Structure
A total of 205 amino acids make up the protein. The prevalent include alpha helices and beta sheets (in red and blue respectively). There are seven serotypes of botulinum neurotoxin that exist, the most likely of which to affect human function being serotype and serotype . Serotype A persists in vivo for months after human intoxication, while serotype E only persists for a few weeks in vivo.
Function
Botulinum neurotoxin (BoNT) consists of a heavy chain and a light chain that serve different functions. The heavy chain is responsible for the endocytosis of the protein into the presynaptic compartment, while the light chain is responsible for catalytic activity. The protein primarily cleaves SNAP-25, a SNARE protein that, when cut, causes synaptic blockade of neurotransmitter release. Different serotypes of BoNT cleave SNAP-25 at different lengths and have different endocytosis affinities.
Significance
Botulinum neurotoxin is the most lethal substance known to man with the human LD50 as low as 1ng/kg. The synaptic blockade of motor neurons prevents muscle movement and can quickly lead to death by asphyxiation. The potential of botulinum neurotoxin to be aerosolized has led the US to classify BoNTs as one of the six category A bioterrorism agents, the highest threat level that can be assigned.
References
McNutt, P., Celver, J., Hamilton, T., & Mesngon, M. (2011). Embryonic stem cell-derived neurons are a novel, highly sensitive tissue culture platform for botulinum research. Biochemical and biophysical research communications, 405(1), 85-90.
Protein structures taken from PDB (https://www.ebi.ac.uk/pdbe/entry/pdb/1zn3).
