Syringomycin E Channel: A Lipidic Pore Stabilized by Lipopeptide?

Abstract

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.

Bax-type Apoptotic Proteins Porate Pure Lipid Bilayers through a Mechanism Sensitive to Intrinsic Monolayer Curvature

“…A similar mechanism of action has been suggested for a number of viral peptides and bacterial toxins (12)(13)(14)(15)(16)(17). One test of the hypothesis that pores formed by Baxtype proteins are at least partially lipidic is the prediction that lipidic pores by their nature should depend more strongly upon the lipid composition of the membrane than purely proteinaceous pores.…”

“…Both the magainin pore and the syringomycin E pore have been modeled as supramolecular assemblies of lipids and peptides with the shape of a torus having net positive curvature (15)(16)(17). Interestingly, planar membrane destabilization is also thought to occur through expansion of positively curved toroidal-type lipidic pores (9).…”

Voltage‐dependent synchronization of gating of syringomycin E ion channels

“…The fact that the m value is strongly voltage-dependent allows us to speculate that some charged residues in the channel complex control synchronous opening/closure of the small channels in the cluster. This charge might be donated by either SRE, which is positively charged, or lipid molecules that are shown to be involved in the channel formation [26].…”

“…We have previously shown [26] that dipolar ''heads'' of the membrane-forming lipids can provide a significant impact to the voltage gating of the SRE channel. This result, combined with the present observation that channel charges do not significantly affect the cluster behavior, suggests that the impact of lipid dipoles on the cluster opening/closure is possible.…”

Channel-forming activity of syringopeptin 25A in mercury-supported phospholipid monolayers and negatively charged bilayers

“…However, in this case the contribution to the overall lipid charge from PS was small, in view of its low mole fraction. It should be noted that the particular behavior of the SP25A channel at a DPTL/ DOPS tBLM in a solution of 0.1 M KCl, pH 6.8, parallels that of the syringomycin E channel, which is closed at positive transmembrane potentials at a DOPS [43] and a DOPS/DOPE BLM in 0.1 M NaCl, pH 6 [44], while it is open at a DOPS/DOPE BLM in 0.1 M NaCl, pH 2, and at a diphytanoylPC BLM in 0.1 M NaCl, pH 6 [44].…”