Nicotinic acetylcholine receptor at 4.6 Å resolution:: Transverse tunnels in the channel wall
Nicotinic acetylcholine receptor at 4.6 Å resolution:: Transverse tunnels in the channel wall
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DOI：
10.1006/jmbi.1999.2721
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发表时间：
1999-05-14
影响因子：
5.6
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（ACh）受体是一种神经递质门控离子通道，负责神经/肌肉突触处细胞间电信号的快速传递。我们在此报道了该通道处于关闭构象时的4.6埃结构，这是通过对嵌入无定形冰中的电鳐突触后膜管状晶体进行电子显微镜观察确定的。分析是在4K温度下，使用300kV场发射源记录的图像上进行的，结合了来自四个螺旋管家族（-16,6； -18,6； -15,7； -17,5）的数据，并对晶格畸变进行了三维校正。这项研究扩展了先前对同一标本在9埃分辨率下的工作。一些具有功能影响的特征现在有了更清晰的界定。通道的门形成一个狭窄的桥，由不超过一两圈侧链组成，横跨跨膜孔的中部。由扭曲的β -折叠链构成的隧道在通道的细胞外壁中被分辨出来，这些隧道将充满水的前庭与假定的ACh结合口袋相连。在构成通道细胞质壁一部分的α -螺旋段之间，分辨出了一组离子可以流动的狭窄开口。有人认为，细胞外隧道是ACh到达结合口袋的通道，细胞质开口起到过滤器的作用，将阴离子和其他不可渗透的物质排除在孔附近。这两种横向途径可能对实现快速的突触后反应都很重要。（C）1999年学术出版社。
The nicotinic acetylcholine (ACh) receptor is the neurotransmitter-gated ion channel responsible for the rapid propagation of electrical signals between cells at the nerve/muscle synapse. We report here the 4.6 Angstrom structure of this channel in the closed conformation, determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes embedded in amorphous ice. The analysis was conducted on images recorded at 4 K with a 300 kV field emission source, by combining data from four helical families of tubes (-16,6; -18,6; -15,7; -17,5), and applying three-dimensional corrections for lattice distortions. The study extends earlier work on the same specimen at 9 Angstrom resolution.Several features having functional implications now appear with better definition. The gate of the channel forms a narrow bridge, consisting of no more than one or two rings of side-chains, across the middle portion of the membrane-spanning pore. Tunnels, framed by twisted beta-sheet strands, are resolved in the extracellular wall of the channel connecting the water-filled vestibule to the putative ACh-binding pockets. A set of narrow openings through which ions can flow are resolved between a-helical segments forming part of the cytoplasmic wall of the channel. It is suggested that the extracellular tunnels are access routes to the binding pockets for ACh, and that the cytoplasmic openings serve as filters to exclude anions and other impermeant species from the vicinity of the pore. Both transverse pathways are likely to be important in achieving a rapid postsynaptic response. (C) 1999 Academic Press.