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Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A
Author(s) -
OblattMontal Myrta,
Yamazaki Masahito,
Nelson Richard,
Montal Mauricio
Publication year - 1995
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560040806
Subject(s) - ion channel , peptide , chemistry , lipid bilayer , biophysics , neurotoxin , peptide sequence , transmembrane protein , conductance , sequence (biology) , amphiphile , transmembrane domain , crystallography , ion , stereochemistry , amino acid , membrane , biochemistry , biology , receptor , mathematics , organic chemistry , combinatorics , gene , copolymer , polymer
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.