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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 ? subunits triggers a concerted rearrangement in the ligand-binding domain, involving an ~1-Å outward displacement of the extracellular portion of the ? subunit where it interacts with the juxtaposed ends of ?-helices shaping the narrow membrane-spanning pore. The ?-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 ?(?) and ? 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.

SUBMITTER: Unwin N 

PROVIDER: S-EPMC3443390 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Gating movement of acetylcholine receptor caught by plunge-freezing.

Unwin Nigel N   Fujiyoshi Yoshinori Y  

Journal of molecular biology 20120724 5


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  ...[more]

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