人类TRPM8通道的结构
Sergii Palchevskyi1,2, Mariusz Czarnocki-Cieciura1, Giulio Vistoli3
1Laboratory of Protein Structure, International Institute of Molecular and Cell Biology in Warsaw, 02-109, Warsaw, Poland.
Communications biology
|October 19, 2023
概括
研究人员使用冷电子显微镜可视化了人类TRPM8通道的封闭状态. 这为TRPM8通道结构和相互作用提供了洞察力,有助于抗癌药物开发.
科学领域:
- 结构生物学是结构生物学.
- 分子生物物理学的分子生物物理.
- 离子通道研究
背景情况:
- 暂时受体潜力拉斯8 (TRPM8) 是一种非选择性的阴离子通道,被各种刺激激活.
- TRPM8是抗癌药物开发和病理状况管理的重要治疗点.
研究的目的:
- 为了确定人体TRPM8通道在封闭状态中的高分辨率冷电子显微镜结构.
- 阐明TRPM8通道功能的结构基础以及与冰素等配体的相互作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来解决人类TRPM8通道的结构.
- 高分辨率结构分析2.7 Å分辨率.
- 对TRPM孔螺旋的分子建模和比较分析.
主要成果:
- 在封闭状态下,获得了人类TRPM8通道的2.7 Å分辨率的冷电磁结构.
- 获得了N-终端前美拉斯他丁同质区域最完整的模型.
- 与脂质和调节器冰素的相互作用被可视化和建模.
结论:
- 确定的结构提供了封闭的TRPM8通道的详细视图,包括其N端区域和脂质相互作用.
- 在TRPM结构中对孔螺旋形状的分析允许将其分类为封闭状态,不敏感状态和开放状态.
- 这些结构信息对于理解TRPM8通道封锁和设计向治疗来说至关重要.
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
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
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...
2.3K
Thermosensation
30.5K
Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
30.5K
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
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
Ligand-gated Ion Channels
12.4K
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...
12.4K


