开纳酸受体的结构和封闭方式
Shanti P Gangwar1, Maria V Yelshanskaya1, Laura Y Yen1,2
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, United States.
Frontiers in pharmacology
|November 5, 2025
概括
凯纳酸受体 (KARs) 是一种离子转移性谷氨酸受体 (iGluR),对大脑信号传递至关重要. 最近的结构研究揭示了对它们的关和调节的见解,增强了我们对神经元通信的理解.
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) 在哺乳动物中枢神经系统 (CNS) 中调解快速刺激性神经传递.
- 凯纳酸受体 (KARs) 是iGluRs的一个子类,是调节神经元电路和突触可塑性的四重体联离子通道.
- KARs包括GluK1-GluK5子单元,GluK1-GluK3形成同型/异型通道,GluK4-GluK5必须与GluK1-GluK3合作.
研究的目的:
- 审查最近对开纳酸受体 (KARs) 关门和药理学调节的结构性见解.
- 基于结构数据,更深入地了解KARs在突触传输和神经元信号传输中的作用.
主要方法:
- 在各种功能状态下分析KAR域和全长受体的众多已解决的同质和异质结构.
- 将KAR结构与其他IGluR (如AMPA受体) 的结构进行比较.
主要成果:
- 在关闭和激活状态下,KAR结构与其他iGluRs,特别是AMPA受体具有整体相似性.
- 结合激素的非导电状态的KARs采用了与其他iGluRs不同的独特形状.
- 结构数据阐明了功能机制,并解决了KAR生物学中的关键问题.
结论:
- 最近的结构研究提供了对KAR功能机制,关和药理学调制的详细见解.
- 了解KAR结构-功能关系对于破译它们在突触传输和神经过程中的作用至关重要.
相关概念视频
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.7K
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...
3.7K
01:24Non-gated Ion Channels
8.0K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
8.0K
01:26Voltage-gated Ion Channels
10.3K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
10.3K
01:19Ligand-gated Ion Channels
13.9K
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...
13.9K
01:19The Role of Ion Channels in Neuronal Computation
3.6K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.6K
01:12Mechanically-gated Ion Channels
7.5K
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...
7.5K