Miyazawa Atsuo, Fujiyoshi Yoshinori, Unwin Nigel
RIKEN Harima Institute, 1-1-1 Kouto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan.
Nature. 2003 Jun 26;423(6943):949-55. doi: 10.1038/nature01748.
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.
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细胞和肌肉细胞之间的电信号传递。在此,我们展示了通过对晶体突触后膜进行电子显微镜观察获得的封闭孔的原子模型。该孔由一个由5个α螺旋组成的内环塑造,这些α螺旋径向弯曲以形成离子的锥形通道,以及一个由15个α螺旋组成的外环,这些α螺旋相互缠绕并使内环与脂质隔离。门是脂质双层中间的一个收缩性疏水带,由相邻内环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,它会触发孔入口相对两侧蛋白质链的旋转。这些旋转通过内环螺旋传递,并通过将疏水带分开来打开孔。