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. 2014 Oct 28;289(51):35438–35454. doi: 10.1074/jbc.M114.612713

FIGURE 8.

FIGURE 8.

Allosteric models. A, dual allosteric coupling model. The pore has two conformations, closed (C) and open (O). The equilibrium constant for the closed to open reaction is L, defined for resting voltage and temperature sensors. L is voltage- and temperature-independent. The voltage sensor equilibrium between resting (RV) and active (AV) conformations is governed by the constant J = exp(zJ(Vm − V0)F/RT), defined for closed pore and resting temperature sensor. The temperature sensor resting (RT) to active (AT) reaction is controlled by equilibrium constant K = exp(−(ΔH − TΔS)/RT), defined for closed pore and resting voltage sensor. When the voltage sensor is active, the pore opening reaction is favored by the allosteric factor D and the equilibrium constant becomes LD. In the same way, when temperature sensor is active, the pore opening reaction is favored by the allosteric factor C. When both sensors are active, the pore opening equilibrium constant is LCD. Factor E accounts for the interaction between voltage and temperature sensors. The equation for Po is shown in terms of equilibrium constants and allosteric factors. B and C, global fit to steady state data using the model in A. Parameters of the fit are as follows: zJ = 0.80; V0 = 260 mV; L = 6.2 × 10−6; ΔH = −53 kcal mol−1; ΔS = −193 cal mol−1 K−1 (T0 = 3.0 °C); C = 2253; D = 346; E = 2062. The sum of the squared residual was 3.1. D, two-tiered allosteric model. This model has the same number of free parameters as the dual allosteric coupling model but considers the existence of four voltage and four temperature sensors that can be activated independently, and each voltage sensor contributes with equal amounts of energy to displace the closed to open equilibrium. For instance, when the four voltage sensors are in the active state, the closed to open equilibrium constant becomes LD4. Likewise, when the four temperature sensors are in the active conformation, the closed to open equilibrium constant is now LC4. E and F, global fit to steady state data using the model in D. Parameters of the fit are as follows: zJ = 0.37; V0 = 234 mV; L = 4.3 × 10−8; ΔH = −19 kcal mol−1; ΔS = −70 cal mol−1 K−1 (T0 = −1.6 °C); C = 52.3; D = 2.3; E = 60. The sum of squared residual was 2.1.