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Selection of the dimeric sweet taste receptor for surface expression and intersubunit interactions

ABSTRACT: The sweet taste receptor is a heterodimer of two class C G protein-coupled receptors (GPCRs), T1R2 and T1R3. While homologous structures of individual domains have been determined, the architecture of the full length T1R2-T1R3 dimer is unknown. Using random mutagenesis and cell sorting, we identify single point mutations and a C-terminal intracellular retention motif in human T1R2 that modulate surface expression and co-trafficking with T1R3 in a HEK293-derivative cell line. A comprehensive mutational scan of T1R2 based on surface expression of both subunits revealed conserved sites for T1R3 interactions, including surfaces on lobe 1 of the ligand binding domain, cysteine rich domain, and transmembrane helix 6. Using the mutational scan to guide modeling of the T1R2-T1R3 dimer predicts a twisted architecture that can explain how outwards motion of lobes 2 in the ligand-binding domains is translated into reorganization of transmembrane regions, and further predicts that extracellular loops 2 form continuous folded structures with the cysteine-rich domains near the dimer axis. These insights into the putative structural organization of the human sweet taste receptor have general implications for the mechanism of class C GPCRs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115751 | GEO | 2018/12/01

REPOSITORIES: GEO

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