Prediction of dynamic allostery for the transmembrane domain of the sweet taste receptor subunit, TAS1R3.

ABSTRACT: The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to

SUBMITTER: Sanematsu K 

PROVIDER: S-EPMC10070457 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature