AlphaFold2捕捉了电压门通道超级家族中的构造转换
1Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Canberra, ACT 2601, Australia.
Biophysical journal
|August 31, 2025
概括
电压感应域的计算模型揭示了不同的结构状态. 在预测中间和终点结构方面,AlphaFold2具有前景,有助于道功能的研究.
科学领域:
- 生物物理
- 结构生物学
- 计算生物学
背景情况:
- 电压通道是控制电活动的基本膜蛋白.
- 它们的功能依赖于电压感应域 (VSD) 的形状变化.
- 通过实验捕捉各种VSD状态仍然具有挑战性.
研究的目的:
- 探索AlphaFold2在各种功能状态中预测VSD结构的实用性.
- 研究多个序列对齐 (MSA) 在结构预测多样性的影响.
- 模拟伪四边形通道结构并分析形状异质性.
主要方法:
- 使用AlphaFold2为32个电压道超级家族成员生成600个模型.
- 使用MSA输入的部分采样来增强结构多样性.
- 在选定的模型上进行了简短的分子动力学模拟.
- 将预测的结构与现有的冷电子显微镜 (cryo-EM) 数据进行比较.
主要成果:
- AlphaFold2成功预测了各种VSD结构,包括激活,失活和中间形状.
- 在不同的VSD家族中,预测的多样性有所不同.
- 完全伪四边形通道的建模揭示了孔隙和细胞内区域的异质状态.
- 观察到局限的全球形状合,一些模型表现出生理不相容的域状态.
- 简短的MD模拟支持了一些预测的结构的可信性,尽管注意到了一些与冷EM结构的差异.
结论:
- AlphaFold2是一个有价值的工具,用于计算预测多种电压道VSD结构.
- 该方法显示了探索中间形态的潜力,但全球合需要进一步调查.
- 对实验数据的验证对于确认预测模型的结构和功能相关性至关重要.
更多相关视频
12:26Author Spotlight: Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
Published on: June 2, 2023
1.1K
08:54Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
Published on: August 9, 2024
523
相关概念视频
Voltage-gated Ion Channels
8.6K
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...
8.6K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.6K
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...
2.6K
Mechanically-gated Ion Channels
6.7K
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...
6.7K
Ligand-gated Ion Channels
12.7K
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...
12.7K
Electrochemical Gradient and Channel Proteins: An Overview
2.6K
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...
2.6K
Non-gated Ion Channels
7.1K
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....
7.1K
