Ergosterol increases the intermolecular distance of amphotericin B in the membrane-bound assembly as evidenced by solid-state NMR.
Amphotericin B (AmB) exerts its antifungal activity by forming ion-permeable assemblies across lipid bilayers. To investigate AmB-AmB bimolecular interactions in the assembly, we carried out (13)C{(19)F}REDOR experiments using 14-(19)F- and (13)C41-labeled AmBs in sterol-containing and sterol-free palmitoyloleoylphosphatidylcholine (POPC) membranes and measured the average distance between the labeled sites of AmBs in membrane-bound forms. The REDOR results suggested that the intermolecular distance of AmB molecules is significantly increased in the ergosterol membrane as compared with the cholesterol membrane. This sterol-dependent change was supported by the UV spectra of AmB in lipid bilayers, in which the excitonic absorption band arising from the aggregated state of AmB shifted to longer wavelength in ergosterol-containing POPC membrane. The REDOR experiments also disclosed that the head-to-head orientation of AmB is predominant in both of the sterol-containing membranes and AmB-POPC interaction was detected only in the ergosterol membrane. Ergosterol significantly influences the interactions between AmB molecules as well as those between AmB and POPC, which may facilitate formation of ion-permeable channels in ergosterol-containing membrane.
Umegawa
Yuichi
Y
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Matsumori
Nobuaki
N
Oishi
Tohru
T
Murata
Michio
M
D000666:Amphotericin B / Q000737:chemistry*; D055592:Biophysical Phenomena; D002784:Cholesterol / Q000737:chemistry; D004875:Ergosterol / Q000737:chemistry / Q000494:pharmacology*; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000737:chemistry; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013302:Streptomyces / Q000378:metabolism; D014466:Ultraviolet Rays
D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D000666:Amphotericin B; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D004875:Ergosterol