Functional equivalence of the nicotinic acetylcholine receptor transmitter binding sites in the open state
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Tantama-2009-Functional equivalen.pdf
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Author(s)
Tantama, Mathew
Licht, Stuart
Date Issued
May 2009
Journal
Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher
Elsevier B.V.
Citation
Tantama, Mathew, and Stuart Licht. “Functional Equivalence of the Nicotinic Acetylcholine Receptor Transmitter Binding Sites in the Open State.” Biochimica et Biophysica Acta (BBA) - Biomembranes 1788, no. 5 (May 2009): 936–944. © 2009 Elsevier B.V.
Version
Final published version
Abstract
The subunits of the muscle-type nicotinic acetylcholine receptor (AChR) are not uniformly oriented in the resting closed conformation: the two α subunits are rotated relative to its non-α subunits. In contrast, all the subunits overlay well with one another when agonist is bound to the AChR, suggesting that they are uniformly oriented in the open receptor. This gating-dependent increase in orientational uniformity due to rotation of the α subunits might affect the relative affinities of the two transmitter binding sites, making the two affinities dissimilar (functionally non-equivalent) in the initial ligand-bound closed state but similar (functionally equivalent) in the open state. To test this hypothesis, we measured single-channel activity of the αG153S gain-of-function mutant receptor evoked by choline, and estimated the resting closed-state and open-state affinities of the two transmitter binding sites. Both model-independent analyses and maximum-likelihood estimation of microscopic rate constants indicate that channel opening makes the binding sites' affinities more similar to each other. These results support the hypothesis that open-state affinities to the transmitter binding sites are primarily determined by the α subunits.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.bbamem.2009.01.009
