Surface location and orientation of the lantibiotic nisin bound to membrane-mimicking micelles of dodecylphosphocholine and of sodium dodecylsulphate.
The interaction of nisin, a membrane-interacting cationic polypeptide, with membrane-mimicking micelles of zwitterionic dodecylphosphocholine and of anionic sodium dodecylsulphate was studied. Direct contacts have been established through the observation of NOEs between nisin and micelle protons. Spin-labeled DOXYL-stearic acids were incorporated into the two micellar systems. From the paramagnetic broadening effects induced in the 1H-NMR spectrum of nisin it is concluded that the molecule 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 residues are immersed into the micelles and oriented towards the center, whereas the more polar or charged residues have an outward orientation. The micellar systems are considered to model the first step in the mechanism of antimicrobial action of nisin, this step is the binding of nisin to the cytoplasmic membrane of target bacteria. Detailed information on this initial binding step is obtained. Hydrophobic and electrostatic interactions appear to be involved in the nisin-micelle contacts. It is suggested that subtilin, a lantibiotic structurally related to nisin, has a comparable membrane interaction surface.
Van Den Hooven
H W
HW
NSR Center for Molecular Structure, Design and Synthesis, Laboratory of Biophysical Chemistry, University of Nijmegen, The Netherlands.
Spronk
C A
CA
Van De Kamp
M
M
Konings
R N
RN
Hilbers
C W
CW
Van De Van
F J
FJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D003497:Cyclic N-Oxides; D005520:Food Preservatives / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D009561:Nisin / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate; D013113:Spin Labels; D013381:Subtilisins / Q000737:chemistry / Q000235:genetics; D013499:Surface Properties; D013501:Surface-Active Agents; D013816:Thermodynamics
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D003497:Cyclic N-Oxides; D005520:Food Preservatives; D008823:Micelles; D013113:Spin Labels; D013501:Surface-Active Agents; D010767:Phosphorylcholine; D009561:Nisin; C005072:5-doxylstearic acid; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine; D013381:Subtilisins