title: N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization.
abstract: Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Lenea
authors.initials: L
authors.lastname: Nørskov-Lauritsen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Jørgensen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: hbo@sund.ku.dk.
authors.forename: Hans
authors.initials: H
authors.lastname: Bräuner-Osborne
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry*; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004220:Disulfides; C488584:GPRC6A protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Dimerization; Disulfide; G protein-coupled receptor (GPCR); GPRC6A; N-linked glycosylation; Post-translational modification (PTM); Signal transduction