"入口电荷"的运动与G蛋白结合受体中的连接体结合
Yair Ben-Chaim1, Baron Chanda, Nathan Dascal
1Department of Neurobiology, The Hebrew University, Jerusalem, 91904, Israel.
Nature
|October 27, 2006
概括
G蛋白结合受体 (GPCR) 通常不被认为是电压敏感的. 这项研究揭示了GPCRs和肌肉蛋白受体一样,表现出电荷运动,表明它们本质上感知了膜潜能,影响了激动剂结合.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- G蛋白结合受体 (GPCRs) 调解关键的细胞信号通路.
- 虽然GPCR是膜蛋白,但传统上它们并不被认为是电压敏感的.
- 最近的发现表明,膜潜力会影响GPCR活性和激进分子亲和力.
研究的目的:
- 调查GPCR是否本质上对膜电位的变化做出反应.
- 描述GPCR中的电压感应机制.
- 阐明特定受体区域在将电压传感与信号连接中的作用.
主要方法:
- 电生理学记录以检测在肌受体 (m2R和m1R) 中的电荷运动 (门电流).
- 对m2R的电荷电压关系的分析.
- 突变性研究侧重于G蛋白合循环.
主要成果:
- 两个原型的GPCRs,m2和m1肌受体 (m2R和m1R),表现出电荷运动相关的电流,类似于电压门通道.
- m2R的关闭电荷-电压关系与乙胆的电压依赖亲和关系保持一致.
- G蛋白合环对于将电压传感与激素结合亲和力联系起来至关重要.
结论:
- GPCR具有内在的电压感应能力.
- 跨膜潜能与化学信号一起,作为GPCRs的调节信号.
- GPCRs作为电气和化学刺激的双重传感器.
相关概念视频
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
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...
Activation and Inactivation of G Proteins
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 affinity and are together...
GPCRs Regulate Adenylyl Cylase Activity
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 cells.
Two...
Two...
G Protein-coupled Receptors
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...


