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J Mol Biol. 2012 Oct 5;422(5):617-34. doi: 10.1016/j.jmb.2012.07.010. Epub 2012 Jul 24.

Gating movement of acetylcholine receptor caught by plunge-freezing.

Author information

  • 1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. unwin@mrc-lmb.cam.ac.uk

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.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
22841691
[PubMed - indexed for MEDLINE]
PMCID:
PMC3443390
Free PMC Article

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