连接体和传感器对神经素受体1的作用
Austin D Dixon1, Asuka Inoue2, Scott A Robson1
1Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, United States.
Journal of the American Chemical Society
|June 1, 2022
概括
神经受体1 (NTS1) 存在多种构造. 像β-arrestin-1和Gαq这样的配体和传感器会动态地改变这些结构,影响受体激活机制.
科学领域:
- 生物化学
- 结构生物学
- 药理学
背景情况:
- 像神经素受体1 (NTS1) 这样的G蛋白结合受体 (GPCR) 在细胞信号传递中起着至关重要的作用.
- 了解NTS1的动态构造状态是阐明其激活机制的关键.
研究的目的:
- 调查连接体和传感器如何调节溶液中的NTS1结构组合.
- 描述NTS1的构造部分状态和交换动态.
主要方法:
- 在NTS1的跨膜螺旋6上使用-19 (19F) 核磁共振 (NMR) 探测器.
- 进行动态核磁共振实验以分析构造交换过程.
主要成果:
- Apo NTS1存在于至少三个形态子状态 (无活性和两个活性类型) 的平衡中,具有毫秒到秒的时间尺度交换.
- 整体连接物重塑这些子状态的热力学和运动性质.
- 与β-arrestin-1或Gαq的合消除了非活性基质,并诱导了明显的结构变化,其中βArr1选择了先前存在的活性状态,而Gαq诱导了一个新的状态.
结论:
- NTS1激活涉及一个动态的整体结构,而不是一个静态的结构.
- 根据合的传感器,可以通过诱导的适合性或形状选择来影响合激活机制.
- 静态结构模型可能不能完全代表受体的溶液组合和动态.
相关概念视频
The Two-State Receptor Model
2.5K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
The binding affinity of a drug determines its interaction with...
2.5K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.7K
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...
2.7K
Transducer Mechanism: G Protein–Coupled Receptors
2.6K
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,...
2.6K
Ligand-gated Ion Channels
12.8K
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...
12.8K
Ligand Binding Sites
13.6K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
13.6K
Ligand Binding and Linkage
5.0K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.0K


