原生甘氨酸受体的结构和组装机制
Hongtao Zhu1, Eric Gouaux2,3
1Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
Nature
|September 23, 2021
概括
原生甘氨酸受体 (GlyRs) 主要与4α:1β亚单元结合. 这种结构揭示了β子单元如何影响受体功能和药理学.
科学领域:
- 神经科学
- 分子生物学
- 结构生物学
背景情况:
- 甘氨酸受体 (GlyRs) 是关键的Cys循环受体,在中枢神经系统中介导抑制性神经传递.
- 脊髓和脑干中的GlyRs功能障碍与运动障碍有关.
- 对于GlyRs的原生静态度和组装机制的了解仍然很少.
研究的目的:
- 为了确定本地甘氨酸受体的静态度.
- 阐明异构GlyR组合和功能的结构基础.
- 在含有β子单元的GlyR中研究药理变化的结构基础.
主要方法:
- 来自猪脊髓和脑干的原生GlyRs的冷电子显微镜 (冷EM).
- 对受体复合物的高分辨率结构分析.
主要成果:
- 确定主导的本地GlyR静态度为4α:1β.
- 揭示了异构受体内的独特的β(+) -α(-) 接口结构.
- 在β子单元中发现一种独特的氨酸,
- 不完整的GlyR复合物的特征结构,包括α-trimers和α-tetramers.
结论:
- 在原生GlyR中,4α:1β固态度占主导地位.
- 该β子单元的独特结构特征解释了受体对称性和离子通道药理学的改变.
- 对部分组装的受体的结构见解为理解GlyR生物发生提供了框架.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.0K
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...
3.0K
G Protein-coupled Receptors
14.1K
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...
14.1K
Assembly of Signaling Complexes
6.1K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.1K
Transducer Mechanism: G Protein–Coupled Receptors
2.9K
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,...
2.9K
Ligand-gated Ion Channels
13.2K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
13.2K
Cholinergic Receptors: Nicotinic
4.4K
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
4.4K


