经典向内整流器K+通道的PIP2激活的结构基础Kir2.22.2
Scott B Hansen1, Xiao Tao, Roderick MacKinnon
1Laboratory of Molecular Neurobiology & Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
Nature
|August 30, 2011
概括
酸4,5-双酸 (PIP(2)) 通过与Kir2.2通道结合来调节细胞静止膜的潜力. 这种相互作用会导致形状变化,打开内部螺旋门并控制离子流.
科学领域:
- 细胞电生理学 细胞电生理学
- 膜生物物理学 膜生物物理学
- 结构生物学 结构生物学
背景情况:
- 脂质分子,特别是酸4,5-双酸 (PIP(2) 是离子通道活性和细胞电信号的关键调节者.
- PIP(2) 是经典的内向整流器 (Kir2) 通道的关键调节器,影响细胞的静止膜潜力,但其精确的作用机制尚不清楚.
研究的目的:
- 阐明PIP(2) 调节Kir2.2通道活动的分子机制.
- 确定PIP(2) -通道相互作用的结构基础及其对通道封闭的影响.
主要方法:
- 采用X射线晶体学来确定Kir2.2通道的结构,该通道与短链PIP(2) 衍生物复合.
- 结构分析的重点是PIP ((2) 绑定站点及其对通道域和门机制的影响.
主要成果:
- PIP(2) 在Kir2.2通道的跨膜域 (TMD) 和细胞质域 (CTD) 的接口上结合.
- PIP(2) 结合引发了构造变化:扩张链接器收缩,CTD翻译,内部螺旋门打开.
- 一种不同的脂质,二甲醇糖醇酸 (PPA),只与非特定的TMD区域结合,未能诱导CTD参与或通道开放.
结论:
- PIP(2) 通过与Kir2.2通道的特定联结体受体相互作用来控制静止膜潜力,从而诱导显著的结构变化.
- 这种机制类似于神经递质激活离子通道,突出显示了细胞信号传输中的保留原则.
相关概念视频
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:11IP3/DAG Signaling Pathway
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 produces two-second...
01:12Mechanically-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...
01:12Mechanically-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...
01:24Non-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.
01:24Non-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.