激活GIRK2通道透机制的结构洞察力
Dailin Li1, Dingyuan Shi1, Lei Wang1
1Key Laboratory of Environmental Biotechnology (XMUT), Fujian Province University, Xiamen University of Technology, Xiamen 361005, China.
Biochimica et biophysica acta. Biomembranes
|September 22, 2023
概括
通过G蛋白导入的向内调整通道 (GIRK) 调节细胞刺激性. 在GIRK2 R201A中确定了一种涉及4-K+组的多离子透机制,为道病变提供了洞察力.
科学领域:
- 生物物理学的生物物理.
- 分子生物学分子生物学
- 计算化学的计算化学
背景情况:
- 通过G蛋白导入的向内调整 (GIRK) 通道对于调节细胞刺激性至关重要.
- 通过GIRK通道的离子导电受选择性过器和螺旋束交叉等结构约束的控制.
- 以前关于透机制的假设缺乏实验验证和能量表征.
研究的目的:
- 阐明GIRK通道的原子层透机制.
- 调查拟议的4K+占用机制的作用.
- 了解GIRK2 R201A.中的离子导电的能量格局.
主要方法:
- 全原子分子动力学 (MD) 模拟.
- 合量子力学/分子力学 (QM/MM) 的方法.
- 在位地定向的突变发生研究 (R201A,E152,N184).
主要成果:
- 在存在PIP2.2.的情况下,GIRK2 R201A突变体表现出中度导电性.
- 一个4-K+离子复合体主导了通过螺旋束交叉门的导电,作为一个屏蔽机制.
- 突变研究发现E152对这种机制至关重要,促进了离子流入,而N184主要影响了导电效率.
结论:
- GIRK通道导电需要多离子分布,而不仅仅依赖于通道的导电状态.
- 鉴定的多离子透机制为道病变提供了潜在的治疗点.
- 这项研究完善了我们对通过生物通道运输离子的理解.
相关概念视频
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
Non-gated Ion Channels
6.8K
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....
6.8K
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
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
IP3/DAG Signaling Pathway
12.2K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.2K


