STRUCTURE AND FUNCTION OF THE ACETYLCHOLINE RECEPTOR

研究申请的目的是了解 烟碱乙酰胆碱受体（AChR）的结构特征， 将这些结构与受体的功能联系起来。 的 乙酰胆碱结合位点的结构将通过 光亲和标记，以确定光致抗蚀剂的各自贡献。 结合位点的亚基。 衍生自d- 筒箭毒碱、溴化乙锭和芋螺毒素将被设计用于探测 γ亚基和δ亚基对激动剂结合位点的贡献。 AChR初级亚基序列的拓扑结构将通过以下方法分析： 标记暴露在AChR细胞外表面的蛋白质。 将通过分离标记片段来鉴定标记位点 和标记残留物的鉴定。 假定的地点 细胞内暴露的片段A156-179将被特别地评价。 化学交联将用于定义近邻关系 亚基和亚基内的单个氨基酸的差异。

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.