Figure 6. Three general allosteric mechanisms of temperature regulation.

(A) Specialized sensor model. A classical allosteric model where the pore domain is allosterically coupled to a specialized domain whose conformation is temperature-dependent. $∆S_{UO}=$ defines the intrinsic temperature-dependent equilibrium constant for activation of a dedicated thermosensing domain. $M_0$ is the intrinsic equilibrium for pore opening and $L_0$ is the coupling interaction between the thermosensor and pore. Examples of specialized temperature sensors include bacterial sodium channels and Hv1 channels. (B) Polymodal sensor model. A variant of the classical allosteric model wherein the ligand or voltage-sensing domain is also sensitive to temperature. In this example, $\theta$ is the voltage-dependent equilibrium constant whose voltage-dependent activation is also sensitive to temperature. In the engineered temperature-sensitive Shaker mutants, the mutations likely alter the temperature-dependence of voltage-sensor movement. (C) Allosteric modifier model. Here, $Q_0$ defines the calcium binding affinity of the calcium sensor and the primary effect of temperature is to alter the allosteric coupling interaction between the ligand-sensing domain and pore domain.