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首页> 外文期刊>Biochemistry >The Amphotericin B-Ergosterol Complex Spans a Lipid Bilayer as a Single-Length Assembly
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The Amphotericin B-Ergosterol Complex Spans a Lipid Bilayer as a Single-Length Assembly

机译：两性霉素B-Ergosterol复合物作为单长组件跨越脂质双层

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摘要

Amphotericin B (AmB) is a polyene macrolide antibiotic clinically used as an antifungal drug. Its preferential complexation with ergosterol (Erg), the major sterol of fungal membranes, leads to the formation of a barrel-stave-like ion channel across a lipid bilayer. To gain a better understanding of the mechanism of action, the mode of lipid bilayer spanning provides essential information. However, because of the lack of methodologies to observe it directly, it has not been revealed for the Erg-containing channel assembly for many years. In this study, we disclosed that the AmB Erg complex spans a lipid bilayer with a single-molecule length, using solid-state nuclear magnetic resonance (NMR) experiments. Paramagnetic relaxation enhancement by Mn2+ residing near the surface of lipid bilayers induced the depth-dependent decay of C-13 NMR signals for individual carbon atoms of AmB. We found that both terminal segments, the 41-COOH group and C38-C40 methyl groups, come close to the lipid bilayer surfaces, suggesting that the AmB-Erg complex spans a palmitoyloleoylphosphatidylcholine (POPC) bilayer with a single-molecule length. Molecular dynamics simulation experiments further confirmed the stabilization of the AmB-Erg complex as a single-length spanning complex. These results provide experimental evidence of the single-length complex incorporated in the membrane by making thinner a POPC Erg bilayer that mimics fungal membranes.
机译：两性统成蛋白B（AMB）是临床上用作抗真菌药物的多烯大啰啉抗生素。其优先粘合与Ergosterol（ERG），真菌膜的主要甾醇，导致在脂质双层穿过血管层的离子通道。为了更好地了解行动机制，脂质双层跨越的模式提供了基本信息。然而，由于缺乏方法可以直接观察它，因此尚未透露许多年份的频道渠道组件。在该研究中，我们公开了使用固态核磁共振（NMR）实验，amb ERG复合物用单分子长度跨越脂质双层。 Mn2 +驻留在脂质双层表面附近的顺磁性松弛增强诱导为AMB的个体碳原子的C-13 NMR信号的深度依赖性衰减。我们发现，两个末端段，41-COOH基团和C38-C40甲基靠近脂质双层表面，表明AMB-ERG复合物用单分子长度跨越棕榈酰基氯酰磷脂酰胆碱（POPC）双层。分子动力学模拟实验进一步证实了AMB-ERG络合物作为单长的跨越复合物的稳定性。这些结果提供了通过制造模拟真菌膜的POPC ERG双层掺入膜中的单长度复合物的实验证据。

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  • 来源
    《Biochemistry》 |2019年第51期|共9页
  • 作者

    Yamamoto Tomoya; Umegawa Yuichi; Tsuchikawa Hiroshi; Hanashima Shinya; Matsumori Nobuaki; Funahashi Kosuke; Seo Sangjae; Shinoda Wataru; Murata Michio;

  • 作者单位

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

    Nagoya Univ Dept Mat Chem Nagoya Aichi 4648603 Japan;

    Nagoya Univ Dept Mat Chem Nagoya Aichi 4648603 Japan;

    Nagoya Univ Dept Mat Chem Nagoya Aichi 4648603 Japan;

    Osaka Univ Grad Sch Sci Dept Chem 1-1 Machikaneyama Toyonaka Osaka 5600043 Japan;

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  • 正文语种 eng
  • 中图分类 生物化学;
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