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

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Abstract

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.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalBiochemistry
Volume51
Issue number1
DOIs
Publication statusPublished - Jan 10 2012

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Ergosterol
Amphotericin B
Phospholipids
Head
Membranes
Molecular interactions
Ion Channels
Phosphorus

All Science Journal Classification (ASJC) codes

  • Biochemistry

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Head-to-tail interaction between amphotericin b and ergosterol occurs in hydrated phospholipid membrane. / Umegawa, Yuichi; Nakagawa, Yasuo; Tahara, Kazuaki; Tsuchikawa, Hiroshi; Matsumori, Nobuaki; Oishi, Tohru; Murata, Michio.

In: Biochemistry, Vol. 51, No. 1, 10.01.2012, p. 83-89.

Research output: Contribution to journalArticle

Umegawa, Yuichi ; Nakagawa, Yasuo ; Tahara, Kazuaki ; Tsuchikawa, Hiroshi ; Matsumori, Nobuaki ; Oishi, Tohru ; Murata, Michio. / Head-to-tail interaction between amphotericin b and ergosterol occurs in hydrated phospholipid membrane. In: Biochemistry. 2012 ; Vol. 51, No. 1. pp. 83-89.
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