Three-dimensional structure of the lantibiotic nisin in the presence of membrane-mimetic micelles of dodecylphosphocholine and of sodium dodecylsulphate.

The lantibiotic nisin is a cationic, polycyclic bacteriocin of 34 residues, including several unusual dehydro residues and thioether-bridged lanthionines. The primary target of its antimicrobial action is the cytoplasmic membrane. Therefore the conformation of nisin when bound to membrane-mimicking micelles of zwitterionic dodecylphosphocholine and of anionic sodium dodecylsulphate was determined with high-resolution NMR spectroscopy. Structures were calculated on the basis of NMR-derived constraints with the distance-geometry program DIANA and were further refined by restrained energy minimization using X-PLOR. The conformation of nisin complexed to both types of micelles is the same, irrespective of the different polar head-groups of the detergents. The structure consists of two structured domains: an N-terminal domain (residues 3-19) containing three lanthionine rings, A, B and C; and a C-terminal domain (residues 22-28) containing two intertwined lanthionine rings numbered D and E. These domains are flanked by regions showing structural variability. Both domains are clearly amphipathic, a property characteristic for membrane-interacting polypeptides. The structures of the ring systems are better defined than those of the linear segments. The four-residue rings B, D and E of nisin all show a beta-turn structure, which is closed by the thioether linkage. The backbones of the rings B and D form type 11 beta-turns. Ring E resembles a type I beta-turn. Preceding the intertwined rings D (residues 23-26) and E (25-28) another type-II beta-turn is found formed by the residues 21-24, so that the C-terminal domain consists of three consecutive beta-turns. The structures of nisin in the micellar systems differ significantly from the previously determined (and now partially recalculated) structure in aqueous solution [van de Ven, F. J. M., van den Hooven, H. W., Konings, R. N. H. & Hilbers, C. W. (1991) Eur J. Biochem. 202, 1181-1188] in the first lanthionine ring around dehydroalanine 5.