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.
Van Den Hooven
H W
HW
NSR Center for Molecular Structure, Design and Synthesis, Laboratory of Biophysical Chemistry, University of Nijmegen, The Netherlands.
Doeland
C C
CC
Van De Kamp
M
M
Konings
R N
RN
Hilbers
C W
CW
Van De Ven
F J
FJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D005520:Food Preservatives / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009561:Nisin / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D011487:Protein Conformation; D017510:Protein Folding; D012967:Sodium Dodecyl Sulfate; D012996:Solutions; D013501:Surface-Active Agents; D013816:Thermodynamics; D014867:Water
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D005520:Food Preservatives; D008823:Micelles; D012996:Solutions; D013501:Surface-Active Agents; D014867:Water; D010767:Phosphorylcholine; D009561:Nisin; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine