Modulation of PTH1R signaling by an ECD binding antibody results in inhibition of β-arrestin 2 coupling.

ABSTRACT: Parathyroid hormone receptor 1 (PTH1R) belongs to the secretin class of G protein coupled receptors (GPCRs) and natively binds parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP). Ligand binding to PTH1R involves binding to the large extracellular domain (ECD) and the orthosteric pocket, inducing conformational changes in the transmembrane domain and receptor activation. PTH1R regulates bone metabolism, signaling mainly through G_s and G_q/11 G-proteins. Here, we used phage display to generate PTH1R ECD-specific antibodies with the aim of modulating receptor functionality. We identified ECD-scFvhFc, which exhibited high affinity binding to both the isolated ECD and to the full-length receptor in styrene-maleic acid (SMA) lipid particles. Epitope ma

SUBMITTER: Sarkar K 

PROVIDER: S-EPMC6783463 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature