STRUCTURAL ANALYSIS OF THE ALPHA 2 ADRENERGIC RECEPTOR

描述(申请人摘要)本研究的长期目标 努力就是定义影响特异度和效率的因素 异源三聚体G蛋白偶联受体(R)的信号传递 (G)。G蛋白信号转导特异性/效率的主要决定因素 偶联受体是细胞特异性表达的亚型 主要信令实体，R、G和效应器(E)。另一个主要网站 调节信号的特异性/效率在于R-G或G-E 接口，其中这些交互受单元体系结构影响， 调节信号从R向R传递的化学计量学和辅助蛋白 G或G到E。 此应用程序侧重于识别和表征 候选“辅助蛋白(S)”是一种新的、功能强大的激活因子 G蛋白。申请者最近实现了部分提纯 神经母细胞瘤-胶质瘤中的这种蛋白质被称为G-蛋白激活物 细胞杂交种NG108-15。此应用程序的直接目标是 从功能上表征和确定该基因的主要序列 G蛋白激活剂。 具体目标是：1)表征G-蛋白的相互作用 含G蛋白的激活剂；2)G蛋白的功能鉴定 与信号转导事件相关的激活剂；3)确定初级 G蛋白激活剂的序列。 G-蛋白激活剂及相关分子可能调节激活 不依赖于受体或可能是受调控的受体的G蛋白 通过它们影响信号强度和/或持续时间的能力来发送信号 特定的转导途径。这类分子可能调节 信号放大通常观察到的信令事件包括 G蛋白，在需要快速检测的组织中可能具有特殊意义 信号处理或在细胞生长异常的条件下 发展。影响信号的蛋白质的演示 受体下游G蛋白水平的传播呈现一种 理解疾病过程和开发新技术的新前沿 模仿或干扰他们的行为的治疗方法。

DESCRIPTION (Applicant's Abstract) A long term objective of this research effort is to define factors that influence the specificity and efficiency of signal propagation by receptors (R) coupled to heterotrimeric G-proteins (G). A major determinant of signalling specificity/efficiency for G-protein coupled receptors is the cell specific expression of the subtypes of the primary signalling entities, R, G and effector (E). Another major site for regulating signalling specificity/efficiency lies at the R-G or G-E interface where these interactions are influenced by cell architecture, stoichiometry and accessory proteins that regulate signal transfer from R to G or G to E. This application focuses on the identification and characterization of a candidate "accessory protein(s)" that is a novel and powerful activator of G-proteins. The applicants have recently achieved partial purification of the protein, termed the G-protein activator, from the neuroblastoma-glioma cell hybrid NG108-15. The immediate goals of this application are to functionally characterize and determine the primary sequence of the G-protein activator. The SPECIFIC AIMS are: 1) Characterize the interaction of the G-protein activator with G-proteins; 2) Functional characterization of the G-protein activator relative to signal transduction events; 3) Determine the primary sequence of the G-protein activator. The G-protein activator and related molecules may regulated the activation of G-proteins independent of receptors or perhaps regulated receptor signalling via their ability to influence signal intensity and/or duration of specific transduction pathways. Molecules of this class may regulate the signal amplification commonly observed with signalling events involving G-proteins and may be of particular significance in tissues requiring rapid signal processing or under conditions of aberrant cell growth and development. The demonstration of proteins that influence signal propagation downstream from receptor at the level of G-protein presents a new frontier for understanding disease processes and developing novel therapeutics that either mimic or interfere with their actions.