探测离子通道孔孔一次一个质子
Gisela D Cymes1, Ying Ni, Claudio Grosman
1Department of Molecular and Integrative Physiology, Center for Biophysics and Computational Biology, and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Nature
|December 16, 2005
概括
研究人员精确地测量了膜蛋白内可电离残留物的质子化状态. 这提供了影响蛋白质功能和封闭机制的微环境的详细地图.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- 膜蛋白利用可电离的残留物进行关键的结构和功能.
- 在生理条件下确定这些残留物的电离状态在实验上具有挑战性.
研究的目的:
- 研究当地的微环境对可电离残留物质亲和力的影响.
- 描述尼古丁乙胆受体的跨膜孔内的残留特异性微环境.
主要方法:
- 在M2跨膜α-helix沿线工程化特定的可电离残留物 (lysine,histidine, arginine).
- 利用电生理学来检测单个质子的结合-解结合事件作为离子电流波动.
- 对波动进行了动态分析,以确定取决于位置的质子转移速率并计算pK (a) 值.
主要成果:
- 在开放通道状态下,开发了M2螺旋周围的微环境的残留能量描述.
- 量化了工程残留物与散装水相对的质子化所需的多余自由能量.
- 与封闭状态相比,在开放通道构造中发现了最小的M2螺旋旋转.
结论:
- 这项研究提供了一个新的,高分辨率的微环境地图,影响膜蛋白中的可电离残留物.
- 这些发现挑战了被提议的显著M2螺旋旋转作为Cys-loop受体中主要封闭机制.
- 这种方法提供了一个强大的方法来研究膜蛋白的电静态和动态.
相关概念视频
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...
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.
Mechanically-gated Ion Channels
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...
G-Protein Gated Ion Channels
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 organs,...
Sensory organs,...
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.
Mechanically-gated Ion Channels
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...


