G蛋白结合受体的结构和功能
Daniel M Rosenbaum1, Søren G F Rasmussen, Brian K Kobilka
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Palo Alto, California 94305, USA.
Nature
|May 22, 2009
概括
G蛋白结合受体 (GPCRs) 对生理反应和疾病治疗至关重要. 最近的结构研究揭示了GPCR激活和构成性活动的洞察力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- G蛋白结合受体 (GPCR) 是重要的细胞表面受体,参与许多生理过程.
- 由于它们在调解对荷尔蒙,神经递质和环境刺激的反应中的作用,它们是现代治疗中很大一部分的目标.
- 了解GPCR是开发广泛疾病治疗方法的关键.
研究的目的:
- 要总结最近在理解G蛋白结合受体 (GPCRs) 的进展.
- 突出GPCRs在膜蛋白结构和生物学中的重要性.
- 探索从高分辨率结构研究中获得的关于GPCR激活机制的见解.
主要方法:
- 对药理学数据的审查.
- 在体内进行的功能性特征研究.
- 对近期高分辨率结构数据的分析.
主要成果:
- 在过去的30年里,在理解GPCR药理学和体内功能方面取得了重大进展.
- 高分辨率的结构研究已经阐明了GPCR激活的分子机制.
- 通过结构生物学获得了对GPCR构成性活动的洞察力.
结论:
- GPCRs代表了各种疾病的关键治疗点.
- 结构生物学方面的进步为GPCR功能提供了深刻的见解.
- 对GPCRs的持续研究对未来的药物开发有希望.
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...


