Figure 1. AChR structure and function.

a. The Torpedo marmorata AChR (subunit stoichiometry α₂βδγ; pdb accession number 2bg9 ⁸³). In adult mouse AChRs an ε subunit replaces γ. The upper and lower arrows mark the levels of a transmitter binding site (at the subunit interface) and the gate region of the pore. b. Thermodynamic cycle for AChR activation. Horizontal arrows, binding to two equivalent binding sites (A, the agonist); vertical arrows, the gating conformational change (C and O, the closed- and open-channel ensembles of the system). ΔG_O and ΔG₂, the O vs. C energy difference without and with two agonist molecules bound; ΔG_LA and ΔG_HA, the free energy of binding, low and high affinity. From detailed balance, 2ΔG_B=ΔG₂-ΔG₀, where ΔG_B=ΔG_HA-ΔG_LA. ΔG_B is the energy from the affinity change for one agonist that serves to increase the open-channel probability.