对温度敏感的AMPA亚型iGluRs的谷氨酸
Anish Kumar Mondal1,2, Elisa Carrillo3, Vasanthi Jayaraman3,4
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
bioRxiv : the preprint server for biology
|September 16, 2024
概括
离子转移性谷氨酸受体 (iGluRs) 的谷氨酸门与正调节器 (PAM) 效应不同,并且对温度敏感. 这项研究揭示了谷氨酸激活iGluR关闭的独特结构机制.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 离子型谷氨酸受体 (iGluRs) 对于刺激性神经传递至关重要.
- 了解IGluR关门机制对于神经药物开发至关重要.
研究的目的:
- 为了确定iGluRs的正基调制剂 (PAM) 激活状态是否代表本源的谷氨酸关口.
- 阐明谷氨酸诱导iGluR激活和脱敏的结构机制.
主要方法:
- 使用温度分辨率的冷电子显微镜 (cryo-EM).
- 研究了α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid亚型iGluR (AMPAR) 的研究.
主要成果:
- 谷氨酸关门是独特的,并且与PAM诱导的关门不同.
- 谷氨酸受体门对温度敏感,生理温度增强激活和导电性.
- 在谷氨酸激活过程中确定了离子通道螺旋链中保存的结构动图.
- 脱敏涉及二极管对脱和通道门重新折叠.
结论:
- iGluRs的谷氨酸门遵循一个独特的机制,与PAMs不同.
- iGluR门的温度敏感性对生理功能和治疗设计有影响.
- 定义了谷氨酸中介iGluR激活和脱敏的结构基础.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
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...
2.2K
GPCR Desensitization
5.9K
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...
5.9K
G-Protein Gated Ion Channels
4.5K
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...
4.5K
Mechanically-gated Ion Channels
6.3K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.3K
Long-term Potentiation
2.7K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when...
Hebbian LTP
LTP can occur when...
2.7K
Ligand-gated Ion Channels
12.3K
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...
12.3K


