由于其核酸结合域的ATP驱动的紧密二元化,CFTR通道的开放
Paola Vergani1, Steve W Lockless, Angus C Nairn
1Laboratory of Cardiac/Membrane Physiology, The Rockefeller University, New York, New York 10021, USA. paola.vergani@rockefeller.edu
Nature
|February 25, 2005
概括
囊性纤维化跨膜导电调节器 (CFTR) 离子通道在其核酸结合域紧密二元化时打开,由ATP驱动. 这种二元化过程对于调节ABC蛋白中的离子运输至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- ATP结合盒 (ABC) 蛋白质是膜载体.
- 囊性纤维化外膜导电调节器 (CFTR) 是一种独特的ABC蛋白,作为离子通道起作用.
- CFTR的离子通道活性是由其核酸结合域 (NBD) 中的ATP结合和水解调节的.
研究的目的:
- 直接将CFTR的NBD中的ATP介导事件与其离子通道孔的打开和关闭联系起来.
- 调查NBD二分化在CFTR通道关口中的作用.
主要方法:
- 在完整的CFTR分子上进行单通道记录.
- 监测NBD1和NBD2中的特定残留物之间的能量合.
主要成果:
- 在预测的NBD1-NBD2二极管接口上的CFTR残留物之间的能量合与通道门变化.
- 这些残留物在封闭的道中是独立的,但在道打开时会被合起来.
- 由ATP驱动的NBD紧密二分化与离子通道开放直接相关.
结论:
- CFTR核酸结合域的ATP诱导的紧密二元化对于离子通道开放至关重要.
- 对NBD二极管接口的动态重组代表了CFTR关门的关键分子机制.
- 这种机制很可能在ABC蛋白超级家族中得到保护.
相关概念视频
Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
Ion Channels
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Secondary Active Transport
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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.
Facilitated Diffusion
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
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