Gating movement of acetylcholine receptor caught by plunge-freezing
In: Journal of Molecular Biology. Elsevier: London; New York. ISSN 0022-2836; e-ISSN 1089-8638, more |   |
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Marine/Coastal | | Author keywords | acetylcholine receptor; freeze-trapping; asymmetric gating; allostericmechanism; electron microscopy |
| Project | Top | Authors | - Association of European marine biological laboratories, more
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| 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 alpha subunits triggers a concerted rearrangement in the ligand-binding domain, involving an similar to 1-angstrom 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. |
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