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Updated: May 27, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity
Zhangsong Wu1, Chen Qiu2, Yiming Liu2
1Kobilka Institute of Innovative Drug Discovery, Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China; The Huanan Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong, China.
Abstract:
Prolactin-releasing peptide receptor (PrRPR), a notable member of the class A peptide-GPCR (G-protein-coupled receptor) family, regulates diverse physiology functions upon activation by PrRP. Herein, we reveal that PrRPR could engage with not only the Gq/11 pathway but also the Gi/o pathway. We further resolve the structures of the PrRPR-Gq and PrRPR-Gi complexes using cryoelectron microscopy (cryo-EM), with PrRP31 as the endogenous ligand. These high-resolution structures enhance our understanding of PrRPR-ligand interactions, aiding the development of targeted drugs aiming at this crucial peptide-receptor system. Comparing these structures with counterparts of other RF-amide peptide receptors accentuates the crucial function of the RF-amide motif in activating receptors and sheds light on the universal mechanism for RF-amide motif detection by RF-amide receptors. Furthermore, structural and functional analysis indicates that conformational alterations in the intracellular loops (ICLs), along with the "wavy hook" of Gα, may explain the selective coupling of G proteins in PrRPR signaling.
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