在脂质双层中对G蛋白合受体的功能调节
Marina Casiraghi1, Marjorie Damian2, Ewen Lescop3
1Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550) , 13 rue Pierre et Marie Curie, F-75005 Paris, France.
Journal of the American Chemical Society
|August 5, 2016
概括
G蛋白结合受体 (GPCRs) 通过多种构造信号. 连接物和膜固醇调节这些状态,影响G蛋白激活,并揭示了GPCR信号的关键合机制.
科学领域:
- 结构生物学
- 生物化学
- 分子药理学
背景情况:
- 了解G蛋白合受体 (GPCR) 信号需要绘制它们的结构格局.
- 膜环境对GPCR结构动态的影响对于信号转导至关重要.
- 列克B4受体2 (BLT2) 是一种具有代表性的GPCR,其信号传递机制令人感兴趣.
研究的目的:
- 为了研究BLT2受体的形状.
- 确定膜环境和连接体如何影响BLT2构造.
- 阐明受体构成,膜组成和G蛋白激活之间的关系.
主要方法:
- 开发一种结合溶液状态核磁共振 (NMR) 光谱的新方法.
- 实施有效的同位素标记方案,以提高NMR信号的检测.
- 用于基于膜的研究,将BLT2受体复合为脂质双层.
主要成果:
- 获得的直接证据表明,未结合的BLT2受体存在四种不同的构造状态.
- 发现结合激素和膜固醇含量能调节这些构造状态的分布.
- 受体构成的变化直接与受体激活其相关G蛋白的能力的变化相关.
结论:
- 在膜环境中,BLT2受体表现出复杂的多态形态.
- 在联体结合,膜组合和下游信号之间存在构造性合.
- 这种合机制可能是GPCR信号传递过程的基础.
相关概念视频
G Protein-coupled Receptors
19.0K
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...
19.0K
G Protein-coupled Receptors
2.3K
2.3K
Activation and Inactivation of G Proteins
12.1K
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...
12.1K
Transducer Mechanism: G Protein–Coupled Receptors
7.0K
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,...
GPCRs are also called heptahelical,...
7.0K
G-protein Coupled Receptors
133.7K
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.
133.7K
G-protein Coupled Receptors
6.5K
6.5K


