Gating Movement of Acetylcholine Receptor Caught by Plunge-Freezing

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• 作者：Nigel Unwin ; Yoshinori Fujiyoshi
• 关键词：ACh ; acetylcholine ; AChBP ; acetylcholine-binding protein ; FSC ; Fourier shell correlation ; CMS ; congenital myasthenic syndrome ; PDB ; Protein Data Bank
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 出版时间：5 October, 2012
• 年：2012
• 卷：422
• 期：5
• 页码：617-634
• 全文大小：3097 K

文摘

The nicotinic acetylcholine (ACh) receptor converts transiently to an open-channel form when activated by ACh released into the synaptic cleft. We describe here the conformational change underlying this event, determined by electron microscopy of ACh-sprayed and freeze-trapped postsynaptic membranes. ACh binding to the ¦Á subunits triggers a concerted rearrangement in the ligand-binding domain, involving an ~ 1©\? outward displacement of the extracellular portion of the ¦Â subunit where it interacts with the juxtaposed ends of ¦Á-helices shaping the narrow membrane-spanning pore. The ¦Â-subunit helices tilt outward to accommodate this displacement, destabilising the arrangement of pore-lining helices, which in the closed channel bend inward symmetrically to form a central hydrophobic gate. Straightening and tangential motion of the pore-lining helices effect channel opening by widening the pore asymmetrically and increasing its polarity in the region of the gate. The pore-lining helices of the ¦Á_¦Ã and ¦Ä subunits, by flexing between alternative bent and straight conformations, undergo the greatest movements. This coupled allosteric transition shifts the structure from a tense (closed) state toward a more relaxed (open) state.