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Seeing a neurotoxin's deadly grip

Two Howard Hughes Medical Institute research teams working independently have discovered new information about how the botulinum neurotoxin shuts down neurons with deadly efficiency. By providing detailed views of the toxin plugged into its neuronal receptor, the new studies could aid efforts to engineer specialized versions of the powerful neurotoxin that is used to treat a wide array of medical problems.

The two groups were led by HHMI investigators Axel Brunger at Stanford University and Edwin Chapman at the University of Wisconsin at Madison. They published their findings December 13, 2006, in advance online publications in the journal Nature.

"Botulinum neurotoxins are powerful tools for biologists and find widespread use as therapeutics for the treatment of certain nervous-system diseases," wrote Giampietro Schiavo of the London Research Institute in an accompanying News & Views commentary in Nature. "For these reasons, the papers reported here are of tremendous value."

Botulinum neurotoxins are among the most deadly natural toxins in the world. They act by first attaching themselves to receptors on the surface of neurons. The toxins then insinuate an enzyme into the neuron that degrades key proteins required for neurons to communicate with one another. The toxins principally affect muscle-controlling motor neurons activated by the neurotransmitter acetylcholine. They kill by paralyzing the respiratory muscles. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), called serotypes A through G, with each acting in a slightly different manner. In 2004, Brungers group published an article in Nature detailing how the toxins that cause botulism and tetanus can recognize and attack particular nerve cell proteins at the neuromuscular junction. Researchers knew that the toxins simultaneously bind to two distinct neuronal receptors one a protein and one a sugar-containing lipid called ganglioside but the details of t
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
13-Dec-2006


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