4aq5 | pdb_00004aq5
Gating movement in acetylcholine receptor analysed by time-resolved electron cryo-microscopy (closed class)
Structural highlights
FunctionACHA_TORMA After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Publication Abstract from PubMedThe 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 alpha subunits triggers a concerted rearrangement in the ligand-binding domain, involving an ~1-A outward displacement of the extracellular portion of the beta subunit where it interacts with the juxtaposed ends of alpha-helices shaping the narrow membrane-spanning pore. The beta-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 alpha(gamma) and delta 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. Gating movement of acetylcholine receptor caught by plunge-freezing.,Unwin N, Fujiyoshi Y J Mol Biol. 2012 Oct 5;422(5):617-34. Epub 2012 Jul 24. PMID:22841691[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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