The Botox^® face lifts and botulism disease are both caused by a neurotoxin from the bacterium Clostridium botulinum. The toxin, often described as the most lethal substance known, is a member of the clostridal neurotoxins (CNTs) group, which block muscle contractions. When injected into someone's face, the effect is a lessening of wrinkles. When ingested, the toxin paralyzes muscles, including those of the internal organs, causing sickness and death. The toxin is also used in medicine for conditions such as uncontrolled blinking, lazy eye, and involuntary muscle contractions.

Nerve cells cause muscles to move by delivering the neurotransmitter acetylcholine into muscle cells. CNTs paralyze muscles by blocking acetylcholine delivery. CNTs enter nerve cells then find and cut SNARE proteins, the machinery responsible for acetylcholine delivery. The inactivation of nerve cells lasts for three to six months.

Breidenbach and Brunger of Stanford have used SSRL and SPEAR3 to solve the first crystal structure of a CNT bound to a SNARE. They found extensive contact between the toxin and its target - much more than the typical lock-and-key paradigm. In kinetic experiments based on the crystal structure, the authors found that the toxin wraps the target SNARE protein around itself. This ensures both target specificity and proper positioning for cutting the SNARE. Knowing the structure of the CNT-SNARE interaction furthers understanding of the toxin's mechanism and may lead to drugs that can treat CNT poisoning.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/cnt.html