Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences

Professor of Molecular Membrane Biology



+44 (0)20 7594 3004b.byrne Website




504Sir Ernst Chain BuildingSouth Kensington Campus






BibTex format

author = {Sarkar, K and Joedicke, L and Westwood, M and Burnley, R and Wright, M and McMillan, D and Byrne, B},
doi = {10.1038/s41598-019-51016-z},
journal = {Scientific Reports},
title = {Modulation of PTH1R signaling by an ECD binding antibody results in inhibition of beta-arrestin 2 coupling},
url = {},
volume = {9},
year = {2019}

RIS format (EndNote, RefMan)

AB - 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 Gs and Gq/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 mapping using hydrogen-deuterium exchange mass spectrometry (HDX-MS) indicates that the α1 helix of the ECD is ECD-scFvhFc’s epitope which may partially overlap with the known PTH (1–34) binding site. However, PTH (1–34)-mediated Gs activation is Undisturbed by ECD-scFvhFc binding. In contrast, ECD-scFvhFc potently inhibits β-arrestin-2 recruitment after PTH (1–34)-driven receptor activation and thus represents the first monoclonal antibody to selectively inhibit distinct PTH1R signaling pathways. Given the complexity of PTH1R signaling and the emerging importance of biased GPCR activation in drug development, ECD-scFvhFc could be a valuable tool to study PTH1R signaling bias.
AU - Sarkar,K
AU - Joedicke,L
AU - Westwood,M
AU - Burnley,R
AU - Wright,M
AU - McMillan,D
AU - Byrne,B
DO - 10.1038/s41598-019-51016-z
PY - 2019///
SN - 2045-2322
TI - Modulation of PTH1R signaling by an ECD binding antibody results in inhibition of beta-arrestin 2 coupling
T2 - Scientific Reports
UR -
UR -
UR -
UR -
VL - 9
ER -