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: 5202013
• 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/5202013
• 关键词: G protein; antibody; dimer; protein structure function; receptor coupling; recombinant proteins; site directed mutagenesis; tissue /cell culture; transfection

The guanine-nucleotide binding regulatory proteins (G-proteins) are alpha1beta1gamma1 heterotrimers which function as transmembrane signal transducers by coupling receptor 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 by a betagamma 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 betagamma complex is becoming increasingly apparent in several systems. The present research emphasized the role of the betagamma complex in G-protein-mediated signal transduction. We have used subunit specific peptide antibodies to probe regions of the betagamma 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 betagamma complex in both transient and stable transfected cell systems. These studies may elucidate the contribution of the betagamma 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 作为跨膜信号的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蛋白组成 一个以特异性受体和效应子为特征的多样化家族 相互作用，这反过来又取决于三个结构 组成亚单位。 α亚基结合鸟嘌呤核苷酸， 在效应物调节中具有公认的作用。 β和γ 亚基通过β-γ复合物紧密缔合，所述β-γ复合物包含 单个功能实体，就像α亚基一样， G蛋白与受体相互作用所必需的。 一种效应调节剂， β-γ复合体的作用越来越明显 几个系统。 目前的研究强调了 β-γ复合物在G蛋白介导的信号转导中的作用。 我们有 使用亚单位特异性肽抗体来探测 β-γ复合物对与α-γ复合物的功能相互作用很重要 亚基和监测重组亚基的表达。 定点 诱变已被用于研究组装，加工和效应器 β-γ复合体在瞬态和稳态中的作用 转染的细胞系统。 这些研究可以阐明 β-γ亚单位复合物对受体和效应物的选择性 G蛋白的特征和适应性反应， 激动剂刺激。