Kv1.2通道的冷EM结构,导电和非导电
Yangyu Wu1, Yangyang Yan1, Youshan Yang1
1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States.
eLife
|February 13, 2025
概括
Kv1.2通道的近原子分辨率结构在选择性过器中揭示了不同的离子模式,为道功能和毒素阻断机制提供了新的见解.
科学领域:
- 生物物理学的生物物理.
- 结构生物学 结构生物学
- 分子神经科学 分子神经科学
背景情况:
- 电压通道 (Kv通道) 对于神经元刺激性至关重要.
- Kv1.2通道的选择性过器是离子透和封闭的关键.
- 了解道状态可以告知药物开发和疾病机制.
研究的目的:
- 以高分辨率冷电子显微镜 (cryoEM) 确定Kv1.2在各种功能状态中的结构.
- 在不同的条件下,研究选择性过器内的离子占用模式.
- 阐明毒素阻断和通道失活的分子机制.
主要方法:
- 接近原子分辨率的冷电子显微镜 (cryoEM) 在2.53.2 Å分辨率.
- 在名义上是零膜电位的洗剂小粒中对Kv1.2的结构分析.
- 开放,C型无活化,毒素结合和结合状态的表征.
主要成果:
- 在不同状态的Kv1.2选择性过器中观察到不同的离子占用模式.
- 阿尔法-登德罗毒素结合部分破坏了最外层的离子结合部位,导致离子密度发生变化.
- 与结合的Kv1.2呈现出一个完整的选择性过器,每个结合点都有离子,这与预期相反.
结论:
- 选择性过器Kv1.2即使存在离子,也保持稳定性.
- 毒素结合会诱导特定的形状变化,影响过器内的离子协调.
- 这些结构为KV通道关,离子选择性和毒素相互作用机制提供了关键的见解.
关键词:
生物物理学的生物物理学.冰冷化EMEM可以使用.丹德罗毒素是一种毒素.没有激活的失活.离子选择性的离子选择性.分子生物物理学分子生物物理学神经科学 神经科学鼠标 鼠标 鼠标 鼠标 鼠标结构生物学结构生物学电压传感器是一个电压传感器.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
19.0K
08:11Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
Published on: November 11, 2022
2.7K
相关概念视频
Voltage-gated Ion Channels
7.9K
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...
7.9K
The 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
Non-gated Ion Channels
6.7K
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....
6.7K
Ion Channels
86.1K
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
86.1K
Mechanically-gated Ion Channels
6.2K
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...
6.2K
Cryo-electron Microscopy
3.2K
Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
3.2K
