Unwin Nigel
MRC Laboratory of Molecular Biology, Cambridge, UK.
Novartis Found Symp. 2002;245:5-15; discussion 15-21, 165-8.
The structure of the acetylcholine-gated channel, trapped in open as well as closed states, has been analysed by electron crystallographic methods. The channel has large vestibules extending from the membrane which shape the acetylcholine-binding pockets and facilitate selective transport of cations across a narrow membrane-spanning pore. When acetylcholine enters these pockets it triggers a concerted conformational change that opens the pore by destabilizing a gate in the middle of the membrane made by a ring of pore-lining alpha-helical segments. The alternative 'open' configuration of porelining segments reshapes the lumen and creates new surfaces, allowing the ions to pass through. Recent results, at nearly 4A resolution, have defined more precisely the structure of the pore and the design of the vestibular entrances.
已通过电子晶体学方法分析了处于开放和关闭状态的乙酰胆碱门控通道的结构。该通道具有从膜延伸出的大前庭，其塑造了乙酰胆碱结合口袋，并促进阳离子通过狭窄的跨膜孔进行选择性运输。当乙酰胆碱进入这些口袋时，它会引发协同构象变化，通过破坏由孔内衬α螺旋段环形成的膜中间的门的稳定性来打开孔。孔内衬段的另一种“开放”构型重塑了管腔并产生新的表面，使离子能够通过。最近接近4埃分辨率的结果更精确地定义了孔的结构和前庭入口的设计。
