通过RGS蛋白调节G蛋白的全球地图
Ikuo Masuho1, Santhanam Balaji2, Brian S Muntean1
1Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Cell
|October 2, 2020
概括
调节G蛋白信号传递 (RGS) 蛋白通过禁用Gα子单元来控制G蛋白信号传递. 这项研究揭示了管理RGS-Gα识别和选择性的规则,推进了分子识别原则.
科学领域:
- 生物化学
- 分子生物学
- 基因组学
背景情况:
- 调节G蛋白信号传递 (RGS) 蛋白质通过不激活G蛋白α子单元 (Gα) 来控制G蛋白信号传递途径至关重要.
- 哺乳动物基因组包含20种正规RGS蛋白和16种Gα蛋白,它们在各种生理过程和疾病中起着重要作用.
研究的目的:
- 阐明RGS蛋白及其Gα基质之间选择性相互作用的原则.
- 了解RGS-Gα识别和选择性的结构基础.
- 为设计具有量身定制的RGS蛋白提供一个框架.
主要方法:
- 在活细胞中利用实时运动测量来评估所有正规的人类RGS蛋白的催化活性.
- 对一组完整的Gα基质检查了RGS蛋白的选择性.
- 使用祖先重建来探索RGS-Gα选择性的进化轨迹.
主要成果:
- 确定了指导RGS-Gα识别和选择性的特定规则.
- 揭示了这种选择性相互作用的结构基础.
- 证明了RGS蛋白质中自然存在的遗传变异如何调节信号.
- 展示了设计选择性的RGS蛋白质的潜力.
结论:
- 这些发现为解读RGS-Gα相互作用中的信号选择性提供了全面的蓝图.
- 这项研究促进了对生物系统分子识别原理的基本理解.
- 这项研究提供了基因变异对信号通路的功能影响的见解.
相关概念视频
Activation and Inactivation of G Proteins
9.6K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
9.6K
GTPases and their Regulation
9.5K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.5K
GTPases and their Regulation
2.7K
2.7K
Small GTPases - Ras and Rho
5.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.0K
GPCRs Regulate Adenylyl Cylase Activity
6.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.6K
G Protein-coupled Receptors
15.5K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
15.5K


