Acetylcholine Receptor Channels Activated by a Single Agonist Molecule |
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Authors: | Archana Jha |
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Institution: | Department of Physiology and Biophysics, State University of New York, Buffalo, New York |
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Abstract: | The neuromuscular acetylcholine receptor (AChR) is an allosteric protein that alternatively adopts inactive versus active conformations (R↔R∗). The R∗ shape has a higher agonist affinity and ionic conductance than R. To understand how agonists trigger this gating isomerization, we examined single-channel currents from adult mouse muscle AChRs that isomerize normally without agonists but have only a single site able to use agonist binding energy to motivate gating. We estimated the monoliganded gating equilibrium constant E1 and the energy change associated with the R versus R∗ change in affinity for agonists. AChRs with only one operational binding site gave rise to a single population of currents, indicating that the two transmitter binding sites have approximately the same affinity for the transmitter ACh. The results indicated that E1 ≈ 4.3 × 10−3 with ACh, and ≈1.7 × 10−4 with the partial-agonist choline. From these values and the diliganded gating equilibrium constants, we estimate that the unliganded AChR gating constant is E0 ≈ 6.5 × 10−7. Gating changes the stability of the ligand-protein complex by ∼5.2 kcal/mol for ACh and ∼3.3 kcal/mol for choline. |
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