Computational Study Of Nisin Interaction With Model Membrane

Nisin is a 34-residue lantibiotic widely used as food preservative. Its mode of
action on the bacterial cytoplasmic membrane is unclear. It should form ion
channels but a molecular description of the interaction between nisin and
phospholipids is lacking. The interactions between nisin and a membrane and the
influence of phospholipids are here analysed by molecular modelling. The NMR
structures of nisin in a micellar environment were previously determined (Van den
Hooven et al., Eur. J. Biochem. 235 (1996) 382-393) Those structures were used to
start with. They were refined by running a Monte Carlo procedure at a model
lipid/water interface. It was shown that nisin is adsorbing onto the interface,
with its N-terminal moiety more deeply inserted in lipids than the C-end,
indicating distinct hydrophobic properties of the N- and C-domains. Therefore, we
suggest that the N-terminal part is implied in the insertion of nisin in lipids,
while the C-terminal moiety could be involved in the initial interaction with the
membrane surface. Modelling the interaction of nisin with different neutral or
anionic phospholipids shows that it disturbs the lipid organisation. The
disturbance is maximal with phosphatidylglycerol. In this system, nisin curves
the surface of phosphatidylglycerol layer round suggesting it could induce
micelle formation. This could be a preliminary step to pore formation. It
suggests that phosphatidylglycerol could have a direct action on nisin insertion
and on ion channel formation. Appearance of a curvature also agrees with the
'wedge model' proposed in the literature for the nisin pore formation.