STRUCTURE OF MOLECULAR ASSEMBLIES INVOLVING MEMBRANES

我们的研究旨在从分子水平上了解 一些涉及膜蛋白的过程，使用物理技术 X射线衍射仪和晶体电子显微镜。 同时，我们正在开发一种新的结构方法-电子 冰冻、潮湿标本的显微镜检查--这将使 分子细节的描述。 工作将集中在以下项目上：(A)缝隙连接通道 以及细胞间的通讯。我们已经了解了第四纪 该通道周围蛋白质的构型和原理 通道可以打开和关闭该通道。我们现在计划扩展这一分析 为了确定哪些部分有助于引起和 控制航道尺寸并与观测到的更紧密地关联 生理学的细节。这些知识将有助于理解 信元-信元通道的设计和通信机制 细胞间的相互作用是受调控的。它最终会为我们提供一个理性的 纠正通信缺陷的基础，如与 恶性组织。(B)乙酰胆碱的四级结构和作用 受体。其中烟碱型乙酰胆碱受体是独一无二的。 受体/通道在一定程度上其生化和 已经确定了药理特性，但几乎没有直接 关于它的四元结构的信息是可用的。我们有 成功地生长了这种分子的管状晶体，我们计划从这里开始 得出第四纪结构图并研究构象 改变。这张地图将提供一个框架，在这个框架上， 基于大量的生化数据可以建立分子图景 (包括氨基酸序列)现已可用。(C)相互作用 核糖体内有细胞膜。核糖核酸的详细图片和 蛋白质在80年代核糖体中的分布正在从电子中显现 含K和Mg2的冰冻晶体阵列的显微观察 解决办法。接下来，我们计划使用这些信息作为 了解功能核糖体颗粒的结构方面 内质网膜和核膜。

Our research is directed towards obtaining a molecular understanding of some processes involving membrane proteins, using the physical techniques of x-ray diffraction and crystallographic electron microscopy. Concurrently, we are developing a new structural approach - electron microscopy of frozen, wet specimens - that will allow more accurate description of the molecular details. Work will focus on the following projects: (a) the gap junction channel and cell-cell communication. We have learned about the quaternary configurations of the protein around this channel and the principle by which the channel may open and close. We plan now to extend this analysis in order to identify the parts which are instrumental in causing and controlling channel dimensions and to relate more closely the observed details to the physiology. This knowledge will help in understanding the design of cell-cell channels and the mechanism by which communication between cells is regulated. It would ultimately provide us with a rational basis for correcting communication defects, as are associated with malignant tissue. (b) Quaternary structure and action of an acetylcholine receptor. The nicotinic acetylcholine receptor is unique among all receptors/channels in the extent to which its biochemical and pharmacological properties have been characterized, yet little direct information is available concerning its quaternary structure. We have succeeded in growing tubular crystals of this molecule from which we plan to derive a map of the quaternary structure and investigate conformational changes. This map would provide the framework upon which a refined molecular picture could be built up based on the extensive biochemical data (including amino acid sequences) now available. (c) Interaction of ribosomes with intracellular membranes. A detailed picture of the RNA and protein distribution in the 80S ribosome is emerging from electron microscopy of crystalline arrays in frozen K+ and Mg2+ containing solutions. We plan next to use this information as a basis for understanding the structural aspects of functioning ribosomal particles on endoplasmic reticulum membranes and the nuclear envelope.