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: 6161989
• 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/6161989
• 关键词: Dictyostelium; G protein; biological signal transduction; dimer; guanine nucleotide binding protein; phospholipase C; protein structure function; receptor coupling; recombinant proteins; site directed mutagenesis; tissue /cell culture; transfection

The guanine-nucleotide binding regulatory proteins (G-proteins) are a1b1g1 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 a subunit binds guanine nucleotides and has a well established role in effector modulation. The b and g subunits are tightly associated as a bg complex, comprising a single functional entity which, like the a subunit, is absolutely required for G-protein interaction with receptor. An effector modulatory role for the bg complex is becoming increasingly apparent in several systems. The present research emphasizes the role of the bg complex in G-protein-mediated signal transduction. During this year the effector functional properties of the Gb5 isoform as well as a series of Gb1 coiled-coil point mutants were studied in transiently transfected COS cells. It was learned that the structurally distinct Gb5 isoform, while competent to regulate PLC-b signalling, was not able to activate the ERK2/MAPK or JNK signalling cascades as Gb1 could. In addition we found that a D20K point mutation in Gb1 facilitated JNK but not PLC-b signalling. Taken together these findings suggest that the mechanism by which Gbg modulates various effector targets differs among the effectors. The findings also implicate the Gbg coiled-coil in the mechanism of JNK activation. These studies may help elucidate the mechanism(s) by which the bg subunit complex modulates structurally diverse effector molecules pursuant to agonist stimulation.

鸟嘌呤核苷酸结合调节蛋白（G蛋白）是 作为跨膜信号转导子的A1 B1 G1异源三聚体 通过将细胞外刺激的受体与细胞内刺激的受体偶联， 效应器（酶、离子通道）。 G蛋白构成了一种多样的 以特异性受体和效应物相互作用为特征的家族 而这又取决于三个组成部分的结构 亚单位。 a亚基结合鸟嘌呤核苷酸， 在效应器调节中的作用。 B和g亚基是 作为BG复合物紧密结合，包含单个功能性 像a亚基一样，是G蛋白绝对需要的实体 与受体的相互作用。 bg的效应调节作用 复杂性在一些系统中变得越来越明显。 的 目前的研究强调BG复合物在 G蛋白介导的信号转导。今年，效应器 Gb 5同种型以及一系列Gb 1的功能特性 在瞬时转染的COS中研究卷曲螺旋点突变体 细胞 据了解，结构上不同的Gb 5同种型，而 有能力调节PLC-b信号传导，不能激活 ERK 2/MAPK或JNK信号级联，如Gb 1所能。 此外，我们还发现， Gb 1中的D20 K点突变促进JNK而不是PLC-b 信号装置. 综合这些发现， Gbg调节各种效应靶点的机制在不同的 效应器 研究结果还表明，Gbg螺旋线圈在 JNK激活机制 这些研究可能有助于阐明 BG亚单位复合物调节结构的机制 根据激动剂刺激的不同效应分子。