通过Ba2+离子封锁和激活BK通道的结构基础
Shubhra Srivastava1, Pablo Miranda1, Teresa Giraldez2
1Molecular Neurophysiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Frontiers in molecular biosciences
|October 3, 2024
概括
离子 (Ba2+) 独特地与大导电 (BK) 通道相互作用,与RCK域和选择性波器结合. 这种结构洞察力解释了Ba2+.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 离子通道研究研究
背景情况:
- 大导电 (BK) 通道对于细胞电生理学,合膜电压和离子度至关重要.
- 离子组成显著影响BK通道功能,离子 (Ca2+) 通过所有导电调节器 (RCK) 域激活通道.
- 离子 (Ba2+) 具有明显的调节作用,据报道,它们通过RCK2激活道,并在选择性过器中阻断的透.
研究的目的:
- 阐明BK通道功能的调节中Ba2+的双重作用背后的结构机制.
- 调查BK通道中Ba2+诱导的特定结合点和构造变化.
主要方法:
- 低温电子显微镜 (Cryo-EM) 用于在存在或缺少Ba2+的情况下确定*Aplysia*BK通道的结构 (PDBIDs:7RJT和7RK6).
- 进行比较结构分析,以确定RCK领域之间的局部变化和协调动态.
- 在选择性过器和RCK领域内分析离子结合点.
主要成果:
- 观察到Ba2+占据了选择性过器中的K+S3位点,在S2和S4位点有K+离子.
- Ba2+离子与RCK1和RCK2域中的高亲密度Ca2+结合位结合,与增加开放概率的功能数据一致.
- 对比结构揭示了RCK1和RCK2域之间在Ba2+结合时的局部构造变化,这表明了协调的动态.
结论:
- 这项研究为Ba2+的双重作用提供了详细的结构基础,它既是BK通道的激活剂,也是BK通道的阻断剂.
- 观察到Ba2+在RCK1,RCK2结合,选择性过器解释了其复杂的调节效应.
- 这些发现有助于更深入地了解二价子对离子通道调节和质调节的作用.
更多相关视频
相关概念视频
01:26Voltage-gated Ion Channels
8.0K
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...
8.0K
01:19Ligand-gated Ion Channels
12.2K
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...
12.2K
01:19The Role of Ion Channels in Neuronal Computation
3.1K
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....
3.1K
01:28Depolarizing Blockers: Mechanism of Action
1.5K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
1.5K
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
469
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
469
01:30Ligand-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