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Study helps explain why botulinum toxin is so deadly

MADISON - A pilot without a map can locate an airport by first finding a nearby landmark, like a big river, and then searching for the airport.

New research from the University of Wisconsin School of Medicine and Public Health (SMPH) and Scripps Research Institute shows how the astonishingly powerful botulinum toxin uses a similar strategy to latch onto nerve cells, the first step in inactivating them.

The research helps explain how the toxin first attaches to a receptor on the surface of a nerve cell, then looks for a second type of receptor that is nearby. Once the toxin links to this second receptor, it can enter the nerve cell and break a protein needed to deliver molecules that can signal other nerve cells.

By blocking this signaling molecule, tiny amounts of botulinum toxin can cause paralysis and even death through respiratory failure. The bacteria that makes this toxin grows in soil, and can be found inside cans of food that were improperly processed. Botulinum toxin is the reason for the extreme danger from bulging cans of food.

Researchers have been working on the unique nerve-blocking ability of the seven individual botulinum toxins for decades, says botulinum expert Edwin Chapman, UW-Madison professor of physiology and a Howard Hughes Medical Institute investigator. "A major question is how the toxin enters neurons," he says.

The research was a close collaboration with Ray Stevens of Scripps, who crystallized the structure that forms when botulinum toxin links to the protein receptor on a nerve cell.

"This is the first paper to show in atomic detail the structure of botulinum neurotoxin touching the receptor on the surface of the neuron," Chapman says. "The toxin has to bind to the neuron it wants to poison. This is a snapshot of the first stage of that poisoning."

The report on the work, in the journal Nature this week, identified a short section on the protein receptor as the exact spot where botulinum toxin
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Contact: Edwin Chapman
chapman@physiology.wisc.edu
608-263-1762
University of Wisconsin-Madison
13-Dec-2006


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