STRUCTURE AND FUNCTION OF THE ACETYLCHOLINE RECEPTOR

研究应用程序的目标是了解 烟碱型乙酰胆碱受体(AChR)和 将这些结构与受体的功能联系起来。这个 乙酰胆碱结合部位的结构将通过 光亲和标记法测定不同来源的 结合部位的亚基。从d-D衍生的光亲和标记 管库拉林、溴化乙锭和芋螺毒素将被设计用来探测 对激动剂结合部位有贡献的伽马亚基和增量亚基。 AChR初级亚基序列的拓扑将通过以下方式进行分析 暴露在AChR胞外表面的蛋白质标记。 标记的位置将通过分离标记的片段来鉴定 以及标记残基的鉴定。推定的地点 细胞内暴露的片段A156-179将被特别评估。 化学交联将被用来定义近邻关系 亚基和亚基内的单个氨基酸。

The objectives of the research application are to understand the structural features of the nicotinic acetylcholine receptor (AChR) and to relate these structures to the function of the receptor. The structure of the acetylcholine binding sites will be investigated by photoaffinity labelling to determine respective contributions of the subunits to the binding sites. Photoaffinity labels derivatized from d- tubocurarine, ethidium bromide and conotoxins will be designed to probe the contributions gamma- and delta-subunits to the agonist binding sites. The topology of the AChR primary subunit sequence will be analyzed by labelling of protein exposed on the extracellular surface of the AChR. The labelled sites will be identified by isolation of labelled fragments and identification of labelled residues. The location of putative intracellularly exposed fragment a156-179 will specifically be evaluated. Chemical crosslinking will be used to define near-neighbor relationships of the subunits and of individual amino acids within subunits.