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 (Synaptosomal-associated protein-25 or SNAP-25) which are essential for synaptic vesicle 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. See Clostridium botulinum neurotoxin serotype A light chain and Botulinum neurotoxin type A (Hebrew).
- 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[2].
- Botulinum neurotoxin type D inhibits the release of TNF from monocytes.
- Botulinum neurotoxin type DC binds and enters efficiently into neurons lacking complex gangliosides. It recognizes only sialic acid but no other gangliosides' moieties[3].
- Botulinum neurotoxin type E, F and G act on human proteins of the neuroexocytosis apparatus.
- Botulinum neurotoxin type X cleaves both canonical and non-canonical vesicle-associated membrane proteins[4].
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. It is used in the treatment of photophobia and Dry Eye[5] and in treatment of individuals with certain pain conditions including migraine[6]. In small quantities CBN can be used as muscle relaxant in cases of spasm and dystonia. CBP type E delivery to the hippocampus ia antiepileptogenic in models of epilepsy[7].
Structural highlights
CBP contains a (LC, residues 1-440, in magenta) and a (HC, residues 441-1296, in cyan) chain. CBP HC contains two modules:
the N-terminal (residues 441-875, in salmon) and the C-terminal (residues 876-1296, in yellow). . [8]
3D structures of botulinum neurotoxin
Botulinum neurotoxin 3D structures
