Head-to-tail interaction between amphotericin b and ergosterol occurs in hydrated phospholipid membrane

Yuichi Umegawa, Yasuo Nakagawa, Kazuaki Tahara, Hiroshi Tsuchikawa, Nobuaki Matsumori, Tohru Oishi, Michio Murata

研究成果: ジャーナルへの寄稿学術誌査読

33 被引用数 (Scopus)


Amphotericin B (AmB) is thought to exert its antifungal activity by forming an ion-channel assembly in the presence of ergosterol. In the present study we aimed to elucidate the mode of molecular interactions between AmB and ergosterol in hydrated phospholipid bilayers using the rotational echo double resonance (REDOR) spectra. We first performed 13C{ 19F}REDOR experiments with C14-19F-labeled AmB and biosynthetically 13C-labeled ergosterol and implied that both "head-to-head" and "head-to-tail" orientations occur for AmB-ergosterol interaction in the bilayers. To further confirm the "head-to-tail" pairing, 13C-labeled ergosterol at the dimethyl terminus (C26/C27) was synthesized and subjected to the REDOR measurements. The spectra unambiguously demonstrated the presence of a "head-to-tail" orientation for AmB-ergosterol pairing. In order to obtain information on the position of the dimethyl terminus of ergosterol in membrane, 13C{ 31P}REDOR were carried out using the labeled ergosterol and the phosphorus atom of a POPC headgroup. Significant REDOR dephasing was observed at the C26/C27 signal of ergosterol in the presence of AmB, but not in the absence of AmB, clearly indicating that the side-chain terminus of ergosterol in the AmB complex comes close to the bilayer surface.

出版ステータス出版済み - 1月 10 2012

!!!All Science Journal Classification (ASJC) codes

  • 生化学


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