N-glycosylation effects on the function of class B1 G protein-coupled receptors

N-glycosylation is one of the most common post-translational modifications and it contributes to proper folding and function of proteins. Class B1 G protein-coupled receptors (GPCRs) are the receptors for peptide hormones that control various body functions and regulate homeostasis. These receptors have a relatively large extracellular domain (ECD) where at least one N-glycosylation site is present. N-glycosylation was reported to enhance pharmacodynamic properties of these receptors such as receptor-ligand binding and receptor activation potency. Here, we summarized N-glycosylation effects of these receptors focusing on cell-surface receptor expression, ligand binding affinity, and receptor activation potency. Receptor N-glycosylation exemplified with calcitonin and amylin receptors apparently enhanced the binding affinity of peptide ligands. Critical N-glycosites that drive whole N-glycosylation effects were reported in the receptors for calcitonin, amylin, calcitonin gene-related peptide, glucose-dependent insulinotropic polypeptide and secretin. In contrast, glucagon-like peptide-1 and corticotropin-releasing factor 1 receptors appear to have each-N-glycosite collectively contribute to the whole-N-glycosylation effects. The potential mechanism of how N-glycosylation enhances the peptide ligand affinity was also addressed. Although there are unexplored receptors that need investigation, N-glycosylation is critical for most of class B1 GPCRs to elicit their normal receptor function. Drug development targeting these receptors should consider the N-glycosylation effects on peptide ligand affinity and receptor activation potency for the accurate evaluation of drug-receptor interaction.