title: Gating movement of acetylcholine receptor caught by plunge-freezing.
abstract: 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 α subunits triggers a concerted rearrangement in the ligand-binding domain, involving an ~1-Å outward displacement of the extracellular portion of the β subunit where it interacts with the juxtaposed ends of α-helices shaping the narrow membrane-spanning pore. The β-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 α(γ) and δ 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.
authors: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. Electronic address: unwin@mrc-lmb.cam.ac.uk.
authors: Nigel
authors: N
authors: Unwin
authors: Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
authors: Yoshinori
authors: Y
authors: Fujiyoshi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D015640:Ion Channel Gating; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D014101:Torpedo
chemical_list: D011950:Receptors, Cholinergic; D000109:Acetylcholine