一个人类的异种-pentameric糖氨酸受体的不对称门
1Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature communications
|October 11, 2023
概括
研究人员揭示了人类甘氨酸受体 (GlyR) 在各种功能状态中的高分辨率结构. 这为神经递质如何激活神经系统功能至关重要的Cys-loop受体提供了关键的见解.
科学领域:
- 神经科学是一个神经科学.
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 赛斯环受体对于神经传递至关重要.
- 了解神经递质激活机制对于药物开发至关重要.
- 在激活状态中缺乏高分辨率结构阻碍了进步.
研究的目的:
- 在所有功能状态下确定人类α1β甘氨酸受体 (GlyR) 的高分辨率结构.
- 阐明Cys循环受体中神经递质激活的结构基础.
主要方法:
- 接近原子分辨率的冷电子显微镜.
- 摄入器的滴定溶解. 摄入器的滴定溶解
- 电生理学记录. 电生理学记录.
主要成果:
- 结构显示在糖氨酸结合后,细胞外域的对称重新排列.
- 跨膜域显示不对称的孔径扩张.
- 跨膜残留物中的电荷分布差异解释了不对称的激活.
结论:
- 甘氨酸结合会诱导不同的细胞外和膜外域动态.
- 对GlyR.的不对称激活机制得到了阐明.
- 为了解Cys-loop受体门的多样性提供了一个框架.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K
Activation and Inactivation of G Proteins
7.2K
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...
7.2K
GPCR Desensitization
6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
G Protein-coupled Receptors
12.2K
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...
12.2K
Transducer Mechanism: G Protein–Coupled Receptors
2.0K
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,...
2.0K


