Pharmacoperone rescue of vasopressin 2 receptor mutants reveals unexpected constitutive activity and coupling bias.

ABSTRACT: Pharmacoperones are small molecules that diffuse into cells and rescue misfolded, mistrafficked protein mutants, restoring their function. These substances act with high target specificity, serving as templates to fold (or refold) receptors, enzymes, ion channels or other proteins and enable them to pass the scrutiny of the cellular quality control system ("rescue"). In the present study we demonstrate that a rescued mutant (L83Q) of the vasopressin type 2 receptor (V2R), shows a strong bias for Gs coupling unlike the WT V2 receptor, which couples to both Gs and Gq/11. Failure of the mutant to couple to Gq/11 was not due to a limiting quantity of G-proteins since other Gq/11-coupled receptors (WT V2R, histamine receptor and muscarinic receptor) responded appropriately to their ligands. Tra

SUBMITTER: Janovick JA 

PROVIDER: S-EPMC5540481 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature