激活异构三分子G蛋白的α子单元的结构决定因素
D G Lambright1, J P Noel, H E Hamm
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510.
Nature
|June 23, 1994
概括
晶体结构分析揭示了GTP结合时转化素α-GDP的结构变化. 这些转移与其他GTPase不同,对于G蛋白信号传递和效应器激活至关重要.
科学领域:
- 结构生物学是结构生物学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 异构三基G蛋白是关键的信号转换器.
- G蛋白α子单元与瓜核酸 (GDP/GTP) 结合,并调节信号通路.
- 了解G蛋白激活机制对于细胞信号研究至关重要.
研究的目的:
- 为了阐明激活时转化素α子单元的构造变化.
- 为了比较不活跃的GDP-bound状态与活跃的GTP-bound状态.
- 了解GTP结合如何影响G蛋白效应因子相互作用.
主要方法:
- 使用X射线晶体学来确定1.8A晶体结构的转素α.GDP.
- 将GDP-bound结构与GTP-gamma S.激活复合物的先前确定结构进行比较.
主要成果:
- 晶体结构揭示了GTP结合时转化素α子单元的明显的构造变化.
- 由GTP的终端酸盐引发的结构变化传播到效应器结合区域.
- 这些激活诱导的变化与在其他GTPase超级家族成员中观察到的不同.
结论:
- 结合GTP会在转化素α子单元中诱导特定的形状重组.
- 这些重新安排对于将激活信号传输到下游效应器至关重要.
- 这些发现提供了对异构三分子G蛋白的独特激活机制的洞察.
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...
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...
Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...


