title: Identification of an ion channel-forming motif in the primary structure of tetanus and botulinum neurotoxins.
abstract: Synthetic peptides with amino acid sequences corresponding to predicted transmembrane segments of tetanus toxin were used as probes to identify a channel-forming motif. A peptide denoted TeTx II, with sequence GVVLLLEYIPEITLPVIAALSIA, forms cation-selective channels when reconstituted in planar lipid bilayers. The single channel conductance in 0.5 M NaCl or KCl is 28 +/- 3 and 24 +/- 2 pS, respectively. In contrast, a peptide with sequence NFIGALETTGVVLLLEYIPEIT, denoted as TeTx I, or a peptide with the same amino acid composition as TeTx II but with a randomized sequence, do not form channels. Conformational energy calculations show that a bundle of four amphipathic alpha-helices is a plausible structural motif underlying observable pore properties. The identified functional module may account for the channel-forming activity of both tetanus toxin and the homologous botulinum toxin A.
authors.affiliation: Department of Biology, University of California San Diego, La Jolla 92093-0319.
authors.forename: M S
authors.initials: MS
authors.lastname: Montal
authors.forename: R
authors.initials: R
authors.lastname: Blewitt
authors.forename: J M
authors.initials: JM
authors.lastname: Tomich
authors.forename: M
authors.initials: M
authors.lastname: Montal
mesh_terms: D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D011487:Protein Conformation; D016415:Sequence Alignment; D013744:Tetanus Toxin / Q000737:chemistry*
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D013744:Tetanus Toxin; D001905:Botulinum Toxins