TY - JOUR
T1 - Formation of a Tight Complex between Amphidinol 3 and Sterols in Lipid Bilayers Revealed by Short-Range Energy Transfer
AU - Hieda, Manami
AU - Tsujimura, Koya
AU - Kinoshita, Masanao
AU - Matsumori, Nobuaki
N1 - Funding Information:
This work was supported by JSPS KAKENHI (JP15H03121, JP16H00773, JP20H04781, and JP20H00405 to N.M.; JP17K15107 and JP20K06590 to M.K.), and JST ERATO (Lipid Active Structure Project).
Publisher Copyright:
© 2022 The Chemical Society of Japan.
PY - 2022/12
Y1 - 2022/12
N2 - The exploration of molecular recognition in lipid bilayers is still extremely difficult. In this report, we leveraged short-range energy transfer (ET) that enabled detection of close contacts within 1 nm distance, and applied it to the interaction of natural products with sterols in lipid bilayers. Amphidinol 3 (AM3), a polyhydroxypolyene metabolite from a marine dinoflagellate, possesses potent antifungal activity by forming membrane pores in a sterol-dependent manner. Although AM3 was shown to interact directly with membrane sterols, the mode of interaction is yet to be fully elucidated. Herein, we found that AM3 and cholestatrienol (CTL), a fluorescent sterol, can be an ET pair because the emission spectrum of the former overlaps with the excitation of the latter. We further confirmed that CTL exerts the sterol-dependent pore formation of AM3 as in the case of cholesterol. Then, titration using intermolecular ET in bilayers revealed that AM3 and CTL form a 1:1 complex with a dissociation constant of 1.4
AB - The exploration of molecular recognition in lipid bilayers is still extremely difficult. In this report, we leveraged short-range energy transfer (ET) that enabled detection of close contacts within 1 nm distance, and applied it to the interaction of natural products with sterols in lipid bilayers. Amphidinol 3 (AM3), a polyhydroxypolyene metabolite from a marine dinoflagellate, possesses potent antifungal activity by forming membrane pores in a sterol-dependent manner. Although AM3 was shown to interact directly with membrane sterols, the mode of interaction is yet to be fully elucidated. Herein, we found that AM3 and cholestatrienol (CTL), a fluorescent sterol, can be an ET pair because the emission spectrum of the former overlaps with the excitation of the latter. We further confirmed that CTL exerts the sterol-dependent pore formation of AM3 as in the case of cholesterol. Then, titration using intermolecular ET in bilayers revealed that AM3 and CTL form a 1:1 complex with a dissociation constant of 1.4
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U2 - 10.1246/bcsj.20220273
DO - 10.1246/bcsj.20220273
M3 - Article
AN - SCOPUS:85147748851
SN - 0009-2673
VL - 95
SP - 1753
EP - 1759
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
IS - 12
ER -
