在Orai1通道的外围TM接口中的水会触发孔隙开放
Valentina Hopl1, Adéla Tiffner1,2, Armin Wutscher1
1Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz, Austria.
Communications biology
|November 16, 2024
概括
在Orai1频道的收费替换.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 离子通道功能 离子通道功能
背景情况:
- 甲状腺1通道是由肌体相互作用分子1 (STIM1) 激活的.
- 道激活涉及复杂的结构调整和门口检查点.
- 外围跨膜域 (TM) 3/TM4接口对于Orai1关口至关重要.
研究的目的:
- 调查Orai1 TM3/TM4接口上的封闭机制.
- 确定改变Orai1通道活动的特定突变.
- 阐明Orai1通道封闭和激活的结构基础.
主要方法:
- 局部定向突变发生,以在Orai1.1中产生充电替代物.
- 功能性测定测量激活T细胞 (NFAT) 转位的核因子.
- 模拟分子动力学以分析通道结构和动力学.
主要成果:
- 在TM3或TM4的中心附近的充电替代产生了构成性活跃的Orai1变体.
- 功能获取与外围TM接口的水分增加相关.
- 增强的水分导致灵活性增加和毛孔开放,模仿STIM1激活.
结论:
- 对外围TM接口的有效脱水对于保持Orai1在封闭状态至关重要.
- 在TM3/TM4接口附近引入电荷会破坏脱水,促进构成性孔隙的开放.
- 这些发现揭示了Orai1通道关门和激活的关键机制.
更多相关视频
相关概念视频
Mechanically-gated Ion Channels
6.2K
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...
6.2K
Aquaporins
4.8K
Aquaporins or AQPs are a family of integral membrane proteins whose primary function is to transport water, while some called aquaglyceroporins also transport glycerol. In addition, aquaporins have also been suspected to be involved in transporting volatile substances, such as carbon dioxide and ammonia, across membranes. Such AQPs that act as gas channels are often highly expressed in cells involved in the gaseous exchange, such as red blood cells, epithelial cells, and pulmonary capillaries.
4.8K
Structure of Porins
2.9K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
2.9K
Porin Insertion in the Outer Mitochondrial Membrane
2.8K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
2.8K
Membrane Fluidity
11.0K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
11.0K
Ligand-gated Ion Channels
12.2K
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...
12.2K


