Every year, millions of people try to look younger by taking injections of Botox, a prescription drug that gets rid of facial wrinkles by temporarily paralyzing muscles in the forehead.
Botox users might be surprised to learn that they're actually receiving minute injections of a bacterial neurotoxin called botulinum, one of the most poisonous substances known.
The botulinum toxin works by invading nerve cells, where it releases an enzyme that prevents muscle contraction.
In recent years, scientists have determined that the enzyme binds to specific sites on proteins called SNAREs, which form a complex in the synapse between nerve and muscle cells.
Without SNAREs, nerves cannot release the chemical signals that tell muscle cells to contract, and paralysis results.
"The botulinum enzyme selectively attacks one of the SNARE proteins and cuts it into two pieces," said Stanford University Professor Axel T. Brunger.
Their results, which will be published in the Dec. 12 online edition of the journal Nature, could help researchers develop alternative treatments for botulism and perhaps find new medical applications for Botox and other neurotoxins.
There are seven forms of botulinum neurotoxin produced by seven different strains of the Clostridium botulinum bacterium, explained Brunger, a Howard Hughes Medical Institute investigator who holds professorships in three Stanford departments---molecular and cellular physiology, neurology and neurological sciences, and the Stanford Synchrotron Radiation Laboratory (SSRL).
Breidenbach, lead author of the study, spent months in Brunger's lab trying to crystallize a SNARE/botulinum A complex for laboratory analysis.
Unfortunately, the botulinum A samples usually ended up slicing the SNARE target in two, rendering it useless.
Often in biology such specificity is accomplished by having large complexes of auxiliary proteins working together, but these bacteria use a very simple mechanism---in this case, a single protein.