STRUCTURAL PREDICTIONS OF THE CHANNEL-FORMING REGION OF BOTULINUM NEUROTOXIN HEAVY-CHAIN

A novel combination of theoretical approaches was exploited to predict which amino acid residues of various botulinum neurotoxin serotypes p articipate in forming ion channels. Estimates of sequence hydrophobic moments were used initially to identify residues within amphipathic re gions in the N-terminal half of the heavy chain. A neural network algo rithm was then used to make additional secondary structural prediction s for these regions. Together, these approaches predicted a compliment ary pattern of four, adjacent amphipathic, possibly transmembrane, reg ions that may be separated by solvent-exposed loops, Both the hydropho bic moment and the neural net analyses predicted that at least one of these amphipathic segments may be in an extended conformation, These t heoretical results are discussed in view of our current knowledge of o ther transmembrane structures.