Structure and gating mechanism of the acetylcholine receptor pore
Structure and gating mechanism of the acetylcholine receptor pore
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DOI：
10.1038/nature01748
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发表时间：
2003-06-26
期刊：
影响因子：
64.8
通讯作者：
Unwin, N
中科院分区：
文献类型：
--
作者：
Miyazawa, A;Fujiyoshi, Y;Unwin, N
烟碱型乙酰胆碱受体通过打开和关闭一个门控的跨膜孔来控制神经和肌肉细胞之间的电信号传递。在这里，我们提出了闭孔的原子模型，通过晶体突触后膜的电子显微镜获得。孔的形状是由5个阿尔法螺旋组成的内环和15个阿尔法螺旋组成的外环形成的，内环呈放射状弯曲，为离子创造了一条逐渐变细的路径，外环相互缠绕，保护内环不受脂质的影响。门是位于脂质双层中间的一条收缩的疏水带，由相邻内螺旋之间的弱相互作用形成。当乙酰胆碱进入配体结合域时，它会触发进入毛孔入口两侧的蛋白质链的旋转。这些旋转通过内部螺旋传递，并通过分开腰带来打开毛孔。
The nicotinic acetylcholine receptor controls electrical signalling between nerve and muscle cells by opening and closing a gated, membrane-spanning pore. Here we present an atomic model of the closed pore, obtained by electron microscopy of crystalline postsynaptic membranes. The pore is shaped by an inner ring of 5 alpha-helices, which curve radially to create a tapering path for the ions, and an outer ring of 15 alpha-helices, which coil around each other and shield the inner ring from the lipids. The gate is a constricting hydrophobic girdle at the middle of the lipid bilayer, formed by weak interactions between neighbouring inner helices. When acetylcholine enters the ligand-binding domain, it triggers rotations of the protein chains on opposite sides of the entrance to the pore. These rotations are communicated through the inner helices, and open the pore by breaking the girdle apart.