GUANINE NUCLEOTIDE BINDING PROTEIN BETA-GAMMA DIMERS--STRUCTURE AND FUNCTION

鸟嘌呤核苷酸结合调节蛋白(G蛋白)是 具有跨膜功能的α(1)β(1)伽马(1)杂三聚体 通过将细胞外刺激受体偶联到 细胞内效应物(酶、离子通道)。G蛋白构成一种 以特定受体和效应器相互作用区分的不同家族 它们又由三个组分的结构决定 亚单位。α亚基与鸟嘌呤核苷酸结合，并有一个井 在效应器调节中的既定角色。β亚基和伽马亚基是 紧密结合为β-伽马络合物，由单一官能团组成 像阿尔法亚单位一样，是G蛋白绝对必需的实体 与受体的相互作用。效应器对β-伽马的调节作用 复杂性在几个系统中变得越来越明显。现在 研究强调了β-伽马复合体在G蛋白中的作用- 中介信号转导。我们已经使用亚单位特异肽 针对β-伽马复合体探测区域的抗体对 与α亚基的功能相互作用并监测其表达 重组亚基。定点突变技术已经被用来研究 β-γ复合体的组装、加工和效应功能 瞬时和稳定的转基因细胞系统。这些研究可能 阐明β-伽马亚单位复合体对 G蛋白的受体和效应器选择性特征及对 激动剂刺激下的适应性反应。

The guanine-nucleotide binding regulatory proteins (G-proteins) are alpha(1)beta(1)gamma(1) heterotrimers which function as transmembrane signal transducers by coupling receptors for extracellular stimuli to intracellular effectors (enzymes, ion channels). G-proteins constitute a diverse family distinguished by specific receptor and effector interactions which in turn are determined by the structure of the three constituent subunits. The alpha subunit binds guanine nucleotides and has a well established role in effector modulation. The beta and gamma subunits are tightly associated as a beta gamma complex, comprising a single functional entity which, like the alpha subunit, is absolutely required for G-protein interaction with receptor. An effector modulatory role for the beta gamma complex is becoming increasingly apparent in several systems. The present research emphasizes the role of the beta gamma complex in G-protein- mediated signal transduction. We have used subunit specific peptide antibodies to probe regions of the beta gamma complex important for functional interaction with the alpha subunit and to monitor expression of recombinant subunits. Site-directed mutagenesis has been used to study the assembly, processing and effector function of the beta gamma complex in both transient and stable transfected cell systems. These studies may elucidate the contribution of the beta gamma subunit complex to the receptor and effector selectivity characteristic of G-proteins and to the adaptive responses pursuant to agonist stimulation.