Botulinum neurotoxin

Function

Botulinum neurotoxin (CBN) is produced by the bacterium Clostridium botulinum. CBP contains a light (residues 1-440) and a heavy (residues 441-875) chains (LC and HC). CBP LC proteolyzes SNARE substrates which are essential for synaptic vescicle fusion and neurotransmitter release thus causing paralysis. CBP HC acts as a channel and as transmembrane chaperone enabling the passage of the LC into the cytosol. ^[1] The bacteria produces 8 neurotoxins which differ in their antigens.

• Botulinum neurotoxin type A is the potent disease agent in botulism.
  
• Botulinum neurotoxin type B is used for treatment of severe spasms in the neck muscles. See Clostridium Botulinum Neurotoxin Type B.
  
• Botulinum neurotoxin type C induces apoptotic cell death in cerebellar neurons acting in birds, mammals and fish.
  
• Botulinum neurotoxin type D inhibits the release of TNF from monocytes.
  
• Botulinum neurotoxin type E, F and G act on human proteins of the neuroexocytosis apparatus.
  

Disease

CBP is the most lethal toxin known causing botulism.

Relevance

CBP type A is used by the cosmetics industry for smoothing wrinkles and is known commercially as Botox. In small quantities CBN can be used as muscle relaxant in cases of spasm and dystonia.

Structural highlights

CBP contains a (LC, residues 1-440, in deeppink) and a (HC, residues 441-1296, in cyan) chains. CBP HC contains two modules: the N-terminal (residues 441-875, in salmon) and the C-terminal (residues 876-1296, in yellow). ^[2]