Redox-regulated ion channel activity of a cysteine-containing gramicidin A analogue.
According to recent data, gramicidin A analogues having positively charged amino acid sequences at the C-termini exhibit two types of channel activity in lipid membranes: classical cation-selective channels and large unselective pores. The induction of unselective pores was shown here to strongly depend on the redox state of the membrane-bathing solution, if the gramicidin analogue contained a cysteine residue in the sequence GSGPKKKRKVC attached to the C-terminus. In particular, the addition of H2O2 led to an increase in the transmembrane current and the loss of cationic selectivity on planar bilayer lipid membranes and an increase in the carboxyfluorescein leakage of liposomes. The effect was observed at high concentration of the peptide while was absent at the single-channel level. It was concluded that oxidation led to possible formation of dimers of the peptide, which promoted the formation of large unselective pores.
Antonenko
Yuri N
YN
Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia. antonen@genebee.msu.ru
Stoilova
Tatyana B
TB
Kovalchuk
Sergey I
SI
Egorova
Natalya S
NS
Pashkovskaya
Alina A
AA
Sobko
Alexander A
AA
Kotova
Elena A
EA
Surovoy
Andrey Y
AY
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry; D003545:Cysteine; D006096:Gramicidin / Q000031:analogs & derivatives*; D006861:Hydrogen Peroxide; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D009842:Oligopeptides / Q000737:chemistry; D010084:Oxidation-Reduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D007473:Ion Channels; D009842:Oligopeptides; D006096:Gramicidin; D006861:Hydrogen Peroxide; D003545:Cysteine