A proximal α-helix of the TGR5 C-Terminus is essential for receptor plasma membrane localization

Introduction: TGR5 is a G-protein coupled bile acid receptor (GPCR), which has been linked to bile acid and glucose homeostasis, energy expenditure and prevention of atherosclerosis. Thus, TGR5 represents an interesting drug target for liver and metabolic diseases. The crystal structure of TGR5 is unknown. We have previously demonstrated that the deletion of the 35 C-terminal amino acids (aa) results in endoplasmic reticulum (ER) retention of the mutated protein (1). The C-terminus of GPCRs is important for G protein-coupling and activation; in addition, the C-termini of several GPCRs are required for correct tr…