SURFACE LOCATION AND ORIENTATION OF THE LANTIBIOTIC NISIN BOUND TO MEMBRANE-MIMICKING MICELLES OF DODECYLPHOSPHOCHOLINE AND OF SODIUM DODECYL-SULFATE

The interaction of nisin, a membrane-interacting cationic polypeptide, with membrane-mimicking micelles of zwitterionic dodecylphosphocholin e and of anionic sodium dodecylsulphnte was studied. Direct contacts h ave been established through the observation of NOEs between nisin and micelle protons. Spin-labeled DOXYL-stearic acids were incorporated i nto the two micellar systems. From the paramagnetic broadening effects induced in the H-1-NMR spectrum of nisin it is concluded that the mol ecule is localized at the surface of the micelles. The interactions of nisin with zwitterionic and with anionic micelles resemble each other as do the nisin conformations [van den Hooven, H. W., Doeland, C. C. M., van de Kamp, M., Konings, R. N. H., Hilbers, C. W. & van de Ven, F . J. M. (1995) Eur. J. Biochem. 235. 382-393]. The hydrophobic residue s are immersed into the micelles and oriented towards the center, wher eas the more polar or charged residues have an outward orientation. Th e micellar systems are considered to model the first step in the mecha nism of antimicrobial action of nisin, this step is the binding of nis in to the cytoplasmic membrane of target bacteria. Detailed informatio n on this initial binding step is obtained. Hydrophobic and electrosta tic interactions appear to be involved in the nisin-micelle contacts. It is suggested that subtilin, a lantibiotic structurally related to n isin, has a comparable membrane interaction surface.