静电识别和诱导适应在kappa-PVIIA毒素与Shaker通道结合
Xiaoqin Huang1, Feng Dong, Huan-Xiang Zhou
1Institute of Molecular Biophysics and School of Computational Science, Department of Physics, Florida State University, Tallahassee, FL 32306, USA.
Journal of the American Chemical Society
|May 5, 2005
概括
这项研究使用布朗动力学 (BD) 和分子动力学 (MD) 揭示了kappa-PVIIA如何与Shaker通道结合. 一个关键的"诱导适合"机制通过原子重组驱动特定的,稳定的复合体形成.
科学领域:
- 结构生物学是结构生物学.
- 计算生物物理学的计算生物物理.
- 分子药理学分子药理学
背景情况:
- 了解蛋白质-蛋白质相互作用对于药物发现至关重要.
- 沙克的通道是各种神经疾病的关键目标.
- 卡帕-PVIIA是一种强大的通道阻塞剂.
研究的目的:
- 为了阐明卡帕-PVIIA与Shaker通道的结合机制.
- 为了确定毒素通道复合体的结构基础.
- 提出一种蛋白质 - 配体结合的一般模型.
主要方法:
- 布朗动力学 (BD) 模拟用于初始对齐.
- 分子动力学 (MD) 模拟用于原子层次重排.
- 静电计算以指导和验证绑定相互作用.
主要成果:
- BD模拟预测了初始的静电引导对齐.
- MD模拟显示了一个2ns的"诱导适合"过程,涉及接口重组.
- 最后的复合物通过静电相互作用 (Lys7),键和疏水相互作用 (Phe9, Phe23) 稳定.
- 突变性分析支持预测的复杂结构.
结论:
- 提出了一种涉及远程静电吸引的通用结合机制,其后是纳米秒级的重新排列.
- 这项研究为kappa-PVIIA通道结合提供了原子层面的见解.
- 这些发现有助于理解通道调节和设计新疗法.
相关概念视频
The Resting Membrane Potential
Overview
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.
Resting Membrane Potential
The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
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...
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...


