Alamethicin-leucine zipper hybrid peptide: a prototype for the design of artificial receptors and ion channels.
In this report, we describe a novel concept of extramembrane control of channel peptide assembly and the eventual channel current modulation. Alamethicin is a peptide antibiotic, which usually forms ion channels in various association states. By introducing an extramembrane leucine zipper segment (Alm-LeuZ), the association number of alamethicin was effectively controlled to produce a single predominant channel open state. The assembly was estimated to be a tetramer, by comparison of the channel conductance with that of the template-assembled Alm-LeuZ tetramer, which was prepared by the conjugation of a maleimide-functionalized peptide template with cysteine-derivatized Alm-LeuZ segments. Employment of an extramembrane segment of a random conformation provided higher levels of channel conductance. The result exemplified the possibility of channel current control by a conformational switch of the extramembrane segments.
Futaki
S
S
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. futaki@scl.kyoto-u.ac.jp
Fukuda
M
M
Omote
M
M
Yamauchi
K
K
Yagami
T
T
Niwa
M
M
Sugiura
Y
Y
D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004553:Electric Conductivity; D007473:Ion Channels / Q000138:chemical synthesis / Q000737:chemistry*; D007476:Ionophores / Q000737:chemistry*; D016350:Leucine Zippers; D008051:Lipid Bilayers / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry*
D007473:Ion Channels; D007476:Ionophores; D008051:Lipid Bilayers; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D000408:Alamethicin