TMEM63蛋白质作为单质高值机械敏感离子通道起作用.
Wang Zheng1, Shaun Rawson2, Zhangfei Shen3
1Departments of Otolaryngology & Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Neuron
|August 5, 2023
概括
机械激活的离子通道TMEM63s意外地作为单体起作用,与相关的OSCA不同. 这种单体形式和IL2链接器的变化影响了它们的高值机械敏感性.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 已知OSCA和TMEM63蛋白质是机械激活 (MA) 离子通道,参与细胞机械传导.
- 通常,OSCA,TMEM16和TMC蛋白质形成具有双孔的同质体,这表明寡合化对它们的功能至关重要.
- 对于TMEM63蛋白质的结构基础和功能影响,特别是它们的寡合体状态,仍然不完全理解.
研究的目的:
- 研究TMEM63蛋白质 (TMEM63A和TMEM63B) 的寡合状态和结构特征.
- 确定TMEM63离子通道的功能性质,包括导电率和激活值.
- 探索细胞内链接器IL2及其在OSCA/TMEM63通道关和寡合化中的进化变异的作用.
主要方法:
- 采用X射线结晶学来确定TMEM63A和TMEM63B的高分辨率结构.
- 电生理学记录 (例如,补丁) 用于分析TMEM63s的机械敏感电流,并设计了OSCA1.2通道.
- 进行了位点定向突变发生,以研究IL2链接器的功能和道关和寡合化中的特定残留物.
主要成果:
- 发现TMEM63A和TMEM63B存在于单体配置,具有单个,高度受限的离子孔.
- 功能分析证实TMEM63s是真诚的机敏离子通道,电导率小,激活值高.
- 对IL2链接器的修改,包括用OSCA1.2 IL2或突变更换,导致单质OSCA1.2通道和升高的MA电流值.
结论:
- TMEM63蛋白质代表了一个独特的单质机械敏感离子通道类别,与二维OSCA不同.
- 细胞内链接器IL2及其结构变异在调节道寡合化和机械敏感度值方面发挥着关键作用.
- 这些发现表明,在OSCA/TMEM63,TMEM16和TMC通道家族中,有保存和分离的门机制.
关键词:
IL2 IL2 IL2 IL2 IL2 IL2 IL2 IL2 IL2 IL2在 OSCA 的 OSCA 里面.在TM6中,我们可以使用TM6.TMC TMC 是一个在TEMEM16中,TEMEM16是TEMEM16的.TMEM63 的意思是什么?在高门的高门.离子通道 离子通道 离子通道机械敏感的机械敏感的氧化聚合物的一种.更多相关视频
08:55Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy
Published on: February 17, 2023
3.2K
12:09Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
Published on: December 31, 2013
10.2K
相关概念视频
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
Ion Channels
87.1K
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...
87.1K
Voltage-gated Ion Channels
8.3K
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...
8.3K
Non-gated Ion Channels
6.9K
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....
6.9K
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K
Tight Junctions
5.3K
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
5.3K
