在BK通道中的电压依赖门的结构基础
Gustavo F Contreras1, Rong Shen1, Ramon Latorre2
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
Nature communications
|July 2, 2025
概括
该研究揭示了和电压激活通道 (BK) 中的和电压传感器如何通信. 结构洞察力解释了BK.
科学领域:
- 分子和细胞神经科学
- 离子通道生理学 离子通道生理学
- 结构生物学 结构生物学
背景情况:
- 和电压激活通道 (BK) 对于刺激细胞中信号集成至关重要.
- BK通道功能依赖于其孔隙,电压传感器和结合部位之间的全性通信.
- 在BK的快速关和电压敏感性背后的分子机制仍然不太清楚.
研究的目的:
- 阐明在Aplysia BK.中电压传感域 (VSD) 和传感器之间的合的机械基础.
- 研究与BK通道激活和结合相关的结构重组.
- 了解BK通道独特关性能的结构决定因素.
主要方法:
- 使用冷电子显微镜 (Cryo-EM) 来确定高分辨率结构.
- 采用位点定向突变发生法,将VSD锁定在特定的构造状态 (激活和静止).
- 研究了含有和不含的结构,观察其对道形状的影响.
主要成果:
- 冷电磁结构揭示了VDS中独特的S4C终端倾斜和关闭电荷侧链运动.
- 静止状态突变体 (R202Q) 提供了一个难以捉摸的完全封闭的BK通道的结构.
- 观察到电压和传感器之间的相互关系,影响孔域构造.
结论:
- 该研究提供了BK通道中电压和传感器之间的能量合的结构证据.
- 这些发现为电压和如何共同调节毛孔领域和BK通道功能提供了一个合理的机制.
- 这些结构阐明了BK通道作为信号集成器的作用的分子基础.
更多相关视频
11:42Reconstitution of a Transmembrane Protein, the Voltage-gated Ion Channel, KvAP, into Giant Unilamellar Vesicles for Microscopy and Patch Clamp Studies
Published on: January 22, 2015
19.2K
08:33Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
Published on: March 11, 2021
2.1K
相关概念视频
Voltage-gated Ion Channels
8.6K
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...
8.6K
The Role of Ion Channels in Neuronal Computation
3.3K
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....
3.3K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.6K
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...
2.6K
Ligand-gated Ion Channels
12.7K
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...
12.7K
Non-gated Ion Channels
7.2K
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....
7.2K
Mechanically-gated Ion Channels
6.7K
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...
6.7K
