Protease activity of botulinum neurotoxin type E and its light chain: cleavage of actin.

We demonstrate here for the first time a proteolytic activity of botulinum neurotoxin type E which is not expressed unless the single chain approximately 150 kDa neurotoxic protein is nicked into the dichain approximately 150 kDa neurotoxin. Actin was cleaved, in vitro, at multiple sites by the dichain neurotoxin and the N-terminal approximately 50 kDa light chain segment isolated from the dichain neurotoxin. The scissile peptide bonds of actin invariably contained Arg or Lys at the P1 site. Proteolytic activity of the isolated light chain and expression of this activity in the dichain form of the neurotoxin are consistent with the light chain's and the neurotoxin's intracellular actions--inhibition of neurotransmitter release.