式通道中通道传导的结构基础
Koichiro E Kishi1, Yoon Seok Kim2, Masahiro Fukuda1
1Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan.
Cell
|February 3, 2022
概括
我们解决了ChRmine的结构, 独特的通道rhodopsin, 这一突破使得神经科学研究的新型光遗传工具的设计成为可能.
科学领域:
- 视觉遗传学
- 结构生物学
- 神经科学
背景情况:
- 道素 (ChRs) 是光门离子通道,对光遗传学至关重要.
- 像ChRmine一样的式CHR表现出不寻常的特性 (大光电流,红移光谱,高光敏感度),但它们的导电机制仍然不清楚.
- 了解Chrmine的结构是阐明其独特功能和开发先进的光遗传工具的关键.
研究的目的:
- 通过高分辨率冷电子显微镜 (cryo-EM) 确定 ChRmine 的结构.
- 阐明 ChRmine 的非典型通道 rhodopsin 特性的结构基础.
- 利用结构见解合理设计具有增强光遗传能力的新型CHR变种.
主要方法:
- 高分辨率 (2.0 Å) 低温电子显微镜 (cryo-EM) 用于确定 ChRmine 的结构.
- 基于结构的蛋白质工程设计ChRmine变体.
- 用于光遗传应用的工程变体的表征.
主要成果:
- ChRmine的2.0 Å冷-EM结构揭示了通道罗多普辛的非典型特征,包括三元组合,短跨膜螺旋3,扭曲的细胞外循环1,大型单体前庭以及三元界面的开口.
- 基于结构信息,成功设计了三种新型的ChRmine变体 (rsChRmine,hsChRmine和frChRmine),表现出进一步的红移光谱,高速动力学或两者的组合.
- 这些工程变体为神经科学中的光遗传应用提供了增强的性能.
结论:
- ChRmine结构提供了前所未有的洞察力,了解式通道罗多普辛的传导和封闭机制.
- 结构导向的设计是创建具有定制性质的下一代通道 rhodopsins 的强大策略.
- 这项工作为开发各种生物应用的先进光遗传工具开辟了新的途径.
更多相关视频
相关概念视频
Channel Rhodopsins
2.7K
Most organisms use photoreceptors to sense and respond to light. Examples of photoreceptors include bacteriorhodopsins and bacteriophytochromes in some bacteria, phytochromes in plants, and rhodopsins in the photoreceptor cells of the vertebral retina. The light-sensitive property of these receptors is because of the bound chromophores, such as bilin in the phytochromes and retinal in the rhodopsins.
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
2.7K
G-Protein Gated Ion Channels
4.9K
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...
4.9K
Electrochemical Gradient and Channel Proteins: An Overview
3.0K
An electrochemical gradient is a fundamental concept in biology and chemistry. It regulates the movement of ions across cell membranes. This movement is influenced by two factors:
The electrical gradient: The electrical gradient across cell membranes refers to the difference in electric charge between the inside and outside of a cell. This difference drives the movement of ions towards or away from the cells. For instance, if the inside of the cell is more negatively charged relative to...
The electrical gradient: The electrical gradient across cell membranes refers to the difference in electric charge between the inside and outside of a cell. This difference drives the movement of ions towards or away from the cells. For instance, if the inside of the cell is more negatively charged relative to...
3.0K
Ligand-gated Ion Channels
12.9K
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...
12.9K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.9K
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...
2.9K
Voltage-gated Ion Channels
8.9K
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...
8.9K


