人类KCNQ1调节和门的结构基础
1Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell
|December 30, 2019
概括
对于身体功能至关重要的KCNQ1通道受到KCNE3和PIP2的调节. 克里奥EM显示KCNE3稳定了通道,而PIP2结合打开了孔隙.
科学领域:
- 分子和细胞生物学
- 生物物理
- 离子通道生理学
背景情况:
- KCNQ1 (Kv7.1) 是一个电压依赖的通道,对胃酸分泌,盐/葡萄糖平衡和心律至关重要.
- 通过与KCNE子单元 (KCNE1-5) 的联合组装来调节组织特异性功能.
- 在不可激发的细胞中,KCNQ1与KCNE3复合,防止在负膜电位处关闭.
研究的目的:
- 阐明KCNE3和PIP2调节KCNQ1通道活动的结构机制.
- 了解PIP2在KCNQ1孔中的作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定KCNQ1- KCNE3复合物的结构.
- 生物化学测定用于评估PIP2对道功能的影响.
主要成果:
- 克里奥EM显示KCNE3的跨膜螺旋与KCNQ1相互作用,可能会将其电压传感器锁定在去极化状态.
- 在没有PIP2的情况下,KCNQ1通道孔仍然封闭.
- PIP2在内膜叶片内与KCNQ1结合,诱导显著的形状变化,导致孔隙大.
结论:
- 通过稳定KCNQ1电压传感器,KCNE3充当调节器.
- PIP2对于KCNQ1通道的开放至关重要,它通过涉及孔口扩张的保存机制起作用.
- 这项研究为辅助子单元和脂质对KCNQ1通道调节提供了原子层面的见解.
相关概念视频
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.6K
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...
3.6K
Voltage-gated Ion Channels
10.1K
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...
10.1K
Ligand-gated Ion Channels
13.8K
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...
13.8K
The 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
Non-gated Ion Channels
7.9K
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....
7.9K
Mechanically-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


