Clostridial botulinum neurotoxins (BoNTs) cause temporary muscle paralysis by blocking neurotransmitter release at presynaptic motor nerve terminals. This effect has led to the rising popularity of Botox injections for reducing the appearance of facial wrinkles, but the mechanism by which the botulinum neurotoxin enters the cytosol is still unknown. In December 2 Nature Structural Biology, Lilia Koriazova and Mauricio Montal at the University of California San Diego, La Jolla, California, USA show how that the botulinium neurotoxin light chain (LC) protease translocates through the heavy chain (HC) channel forming a dynamic structural device similar to conducting/translocating channels of the endoplasmic reticulum and mitochondria (Nature Structural Biology, doi:10.1038/nsb879, December 2, 2002).

Koriazova & Montal used the combined detection of channel currents and substrate proteolysis — the two hallmark activities of BoNTs — to determine if HC channel activity and LC translocation were correlated. They observed...

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