在RCK2中的一个分子开关触发了KNa1.1 (KCNT1) 通道的依赖的激活
Bethan A Cole1, Antreas C Kalli2, Nadia Pilati3
1School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom.
Biophysical journal
|April 12, 2024
概括
与KNa1.1通道结合的 (Na+) 激活了神经元的刺激性. 突变突变发现,残留物D884对Na+激活至关重要,其口袋适应触发了通道开放.
科学领域:
- 神经科学是一个神经科学.
- 离子通道生理学 离子通道生理学
- 分子生物学分子生物学
背景情况:
- 激活Na+的K+通道KNa1.1 (KCNT1基因) 调节神经元刺激性.
- 细胞内Na+结合和道激活的确切机制尚不清楚.
研究的目的:
- 阐明Na+激活过程中KNa1.1的RCK2域中特定残留物的结构和功能作用.
- 为了研究KNa1.1通道门的基础上的形状变化.
主要方法:
- 对KNa1.1通道形状的结构分析 (无活性与Na+激活).
- 在βN-αQ循环和RCK2域内的关键残留物的位点定向突变发生.
- 电生理学记录以评估通道活动和Na+依赖性.
主要成果:
- 突变突变发现,残留物D839和K885参与Na+结合和道激活.
- 用阿拉宁 (D884A) 替换D884,导致独立于Na+的构成性活跃通道.
- 在D884的氨基酸大小依赖的效应表明,βO口袋中的容纳对于Na+依赖的关至关重要.
结论:
- Na+ 结合会诱导一种形状变化,将 D884 置于 βO 囊中.
- 这种适应触发了RCK域的下游构造变化,导致KNa1.1通道激活.
- D884在Na+激活的K+通道的全性关门机制中发挥着关键作用.
相关概念视频
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Voltage-gated Ion Channels
8.2K
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...
8.2K
The Role of Ion Channels in Neuronal Computation
3.2K
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....
3.2K
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
Mechanically-gated Ion Channels
6.4K
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...
6.4K
MAPK Signaling Cascades
5.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K


