一个电压门的通道的晶体结构在两个潜在的失活状态
Jian Payandeh1, Tamer M Gamal El-Din, Todd Scheuer
1Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Nature
|June 9, 2012
概括
使用晶体学揭示了对电压导入 (Na(V)) 通道无活化的结构洞察力. 这些发现揭示了Na(V) 通道封闭机制,并为通道病变提供了新的治疗点.
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学.
- 离子通道功能 离子通道功能
背景情况:
- 电压接 (Na(V)) 通道对于可刺激细胞中的动作潜能启动和传播至关重要.
- 对于控制膜刺激性而言,Na(V) 通道无活化是必不可少的,但它的结构基础仍然不太清楚.
研究的目的:
- 阐明了基础的结构机制Na(V) 道不活化.
- 为了提供高分辨率的结构快照的野生类型的Na(V) 道在非活化的状态.
主要方法:
- 在3.2 Å分辨率的X射线晶体学.
- 野生类型Na(V) Ab通道结构的分析.
- 与之前描述的突变Na(V) Ab通道进行比较.
主要成果:
- 观察到两种不同的野生类型Na(V) Ab通道的非活化状态.
- 在S6螺旋和细胞内激活门中发现了显著的重排.
- 揭示了全球结构不对称性增加,孔隙尺寸改变,电压感应领域转移.
结论:
- 确定的结构为Na(V) 通道封闭和失活机制提供了新的见解.
- 这些发现为开发针对Na(V) 通道病变的药物开辟了新的途径.
相关概念视频
Voltage-gated Ion Channels
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 types of...
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 types of...
Voltage-gated Ion Channels
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 types of...
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 types of...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
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...
Non-gated Ion Channels
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.
Non-gated Ion Channels
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.
Mechanically-gated Ion Channels
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...


