Botox: Toxic medicine

What is it?

Botulinum toxin A –- more commonly known today as Botox – is a neurotoxin produced by the bacterium Clostridium botulinum. It acts on nerves at the point at which they meet the muscles that they control, where it disrupts transmission of chemical messenger molecules causing muscular paralysis. Botulinum toxin is one of the most potent human toxins and C. botulinum infection causes botulism, a serious paralytic illness. Thankfully botulism is rare. More common today is the deliberate localised injection of the toxin for cosmetic purposes, where its paralytic properties can be used to banish wrinkles, laughter lines, and the ability of professional actors to convincingly convey normal human facial expressions. Botox also has a number of important medical applications and is now routinely used to treat eye misalignment (strabismus), excessive sweating (hyperhidrosis), migraine and urinary incontinence, with no side effects upon acting ability yet reported.

What does it look like?

botoxBotulinum toxin A is made up of three functional domains which each play a distinct role in delivery and action of the toxin. The receptor-binding domain (yellow and red) is important for entry into the nerve cells where the toxin is initially encapsulated within a small membrane bordered compartment called an endosome. Next the toxin’s translocation domain (green) induces a pore in the compartment to allow transport of the enzymatic domain (blue) out of the endosome and into the cytoplasm of the cell where it cuts target proteins in the nerve to block chemical messenger release and induce paralysis. This image was generated using PDB ID 3BTA1 and the molecular graphics software PyMOL.

Where did the structure come from?

The crystal structure of botulinum toxin A was first published 1 in the scientific journal Nature in 1998, using toxin isolated from liquid cultures of Clostridium botulinum.

1. Lacy et al., Nature (1998) 5: 898-902

 

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