Activation Dynamics for the Taste Receptor as an Energy Sensor

Sweet-taste receptors play a crucial role in maintaining biological homeostasis by acting as energy sensors. However, the dynamics of this receptor after binding remain unknown because previous studies have primarily examined the static binding of the sweet taste receptor in complex with ligands. This review focuses on the mechanisms underlying the allostery-mediated activation and inactivation of the transmembrane domain of the sweet taste receptor subunit, TAS1R3.

Molecular dynamics simulations predicted that agonist binding induces the opening of the ionic lock formed by transmembrane helices III and VI. These simulations were validated by functional assays in HEK293 cells expressing the sweet taste receptor.

The allostery through the interaction between the transmembrane domain of TAS1R3 and agonist would induce the conformational change on the intracellular side of the receptor, facilitating binding with the Gα subunit.