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

鸟嘌呤核苷酸结合蛋白 β-γ 二聚体——结构和功能

• 批准号: 3840501
• 负责人: W SIMONDS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3840501
• 关键词: G protein; antibody; biological signal transduction; dimer; gene expression; guanine nucleoside; protein structure function; receptor coupling; site directed mutagenesis; tissue /cell culture; transfection

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.

鸟嘌呤核苷酸结合调节蛋白（G蛋白）是 α（1）β（1）γ（1）异源三聚体， 通过将细胞外刺激的受体偶联到 细胞内效应物（酶、离子通道）。 G蛋白构成了 以特异性受体和效应物相互作用为特征的多样化家族 而这又取决于三个组成部分的结构 亚单位。 α亚基结合鸟嘌呤核苷酸， 在效应器调节中的作用。 β和γ亚基是 作为β-γ复合物紧密结合，包含单个功能性 与α亚基一样，G蛋白绝对需要α亚基 与受体的相互作用。 β-γ的效应调节作用 复杂性在一些系统中变得越来越明显。 本 研究强调了β-γ复合物在G蛋白中的作用， 介导的信号转导。 我们使用亚基特异性肽 针对β-γ复合物的探针区域的抗体， 与α亚基的功能性相互作用，并监测 重组亚基。 定点突变已被用于研究 β-γ复合物的组装、加工和效应器功能 瞬时和稳定转染的细胞系统。 这些研究可能 阐明β-γ亚基复合物对 G蛋白的受体和效应物选择性特征， 根据激动剂刺激的适应性反应。