Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A

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Abstract
Synthetic peptides patterned after the predicted transmembrane sequence of botulinum toxin A were used as tools to identify an ion channel‐forming motif. A peptide denoted BoTxATM, with the sequence GAVILLEFIPEIAI PVLGTFALV, forms cation‐selective channels when reconstituted in planar lipid bilayers. As predicted, the self‐assembled conductive oligomers express heterogeneous single‐channel conductances. The most frequent openings exhibit single‐channel conductance of 12 and 7 pS in 0.5 M NaC1, and 29 and 9 pS in 0.5 M KCl. In contrast, ion channels are not formed by a peptide of the same amino acid composition as BoTxATM with a scrambled sequence. Conformational energy calculations show that a bundle of four amphipathic α‐helices is a plausible structural motif underlying the measured pore properties. These studies suggest that the identified module may play a functional role in the ion channel‐forming activity of intact botulinum toxin A.