Molecular Structure of Amphotericin B Channels

两性霉素B是膜离子通道渗透的经典模型化合物之一，尽管该通道的结构尚不清楚。这种多烯大环内酯被认为在脂质膜上形成离子可渗透的孔隙，通过组织成桶状的分子排列，其中极性多元醇区域在中间。然而，通道的大小和性质似乎取决于磷脂膜中存在的甾醇，麦角甾醇或胆固醇。通过研究其离子渗透特性，特别是相关离子（如碱金属系列）的选择性序列，可以揭示其超分子结构。本研究的三个基本目标是：1)获得两性霉素通道在不同磷脂膜和甾醇膜环境下完整的IA族和IIA族金属阳离子和卤化物选择性序列，2)确定这些环境下通道形成的温度依赖性、聚集状态和分子度，3)结合静电分子建模软件使用这些数据，为两性霉素通道结构设计一致的模型。生物膜离子通道在从神经传递到囊性纤维化的许多过程中起着核心作用。这一研究将促进两性霉素通道和离子通道的认识。

One of the classic model compounds for membrane ion channel permeation is Amphotericin B, although the structure of the channel is still unknown. This polyene macrolide is thought to form ion permeable pores in lipid membranes by organizing into a barrel stave like arrangement of molecules with the polar polyol region in the middle. However, the size and nature of the channels seem to vary depending upon which sterol, ergosterol or cholesterol, is present in the phospholipid membrane. The supramolecular structure of such channels may be revealed by studying its ion permeation properties, especially the selectivity sequence of related ions (e.g. the alkali metal series). The three basic goals for this research are: 1)Obtain complete Group IA and IIA metal cation and halide selectivity sequences for Amphotericin channels in different phospholipid and sterol membrane environments, 2) Determine the temperature dependence, aggregation state and molecularity of channel formation in these environments, 3) Using these data in conjunction with electrostatic molecular modeling software, design consistent models for Amphotericin channel structures. %%% Biological membrane ion channels play a central role in many processes from neurotransmission to cystic fibrosis. This research should advance on knowledge of Amphotericin channels and ion channels in general.