Syringomycin E channel: a lipidic pore stabilized by lipopeptide?
Highly reproducible ion channels of the lipopeptide antibiotic syringomycin E demonstrate unprecedented involvement of the host bilayer lipids. We find that in addition to a pronounced influence of lipid species on the open-channel ionic conductance, the membrane lipids play a crucial role in channel gating. The effective gating charge, which characterizes sensitivity of the conformational equilibrium of the syringomycin E channels to the transmembrane voltage, is modified by the lipid charge and lipid dipolar moment. We show that the type of host lipid determines not only the absolute value but also the sign of the gating charge. With negatively charged bilayers, the gating charge sign inverts with increased salt concentration or decreased pH. We also demonstrate that the replacement of lamellar lipid by nonlamellar with the negative spontaneous curvature inhibits channel formation. These observations suggest that the asymmetric channel directly incorporates lipids. The charges and dipoles resulting from the structural inclusion of lipids are important determinants of the overall energetics that underlies channel gating. We conclude that the syringomycin E channel may serve as a biophysical model to link studies of ion channels with those of lipidic pores in membrane fusion.
Malev
Valery V
VV
Institute of Cytology, St. Petersburg, 194064, Russia.
Schagina
Ludmila V
LV
Gurnev
Philip A
PA
Takemoto
Jon Y
JY
Nestorovich
Ekaterina M
EM
Bezrukov
Sergey M
SM
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000737:chemistry; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D013997:Time Factors
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000900:Anti-Bacterial Agents; D004573:Electrolytes; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D010456:Peptides, Cyclic; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C105246:syringomycin E; C017251:1,2-oleoylphosphatidylcholine; D002118:Calcium