생화학분자생물학회

	Hee-Jung Choi ( choihj@snu.ac.kr )
	2021~present	Professor, Dept. of Biological Sciences, Seoul National University, Seoul, Korea
	2016~2021	Associate Professor, Dept. of Biological Sciences, Seoul National University, Seoul, Korea
	2012~ 2016	Assistant Professor, Dept. of Biological Sciences, Seoul National University, Seoul, Korea
	2003~2012	Research Associate, Depts. of Structural Biology / Molecular & Cellular Physiology, Stanford University, Stanford, CA, USA
	2000~2003	Postdoc, Dept. of Structural Biology, Stanford University, Stanford, CA, USA
	1997~2000	Postdoc, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
	1987~1997	BS/ MS/ PhD, Dept. of Chemistry, Seoul National University, Seoul, Korea

Structural insights into GPCR signaling activated by peptide ligands: from molecular mechanism to therapeutic application

Recent advances in structural biology have profoundly enhanced our understanding of G protein-coupled receptors (GPCRs), providing detailed molecular insights into their activation and ligand recognition. Here, in this Review, we explore the molecular mechanisms of class A and class B GPCRs bound to peptide agonists and their implications for drug development. We examine representative GPCRs, such as the angiotensin II type 1 receptor, chemokine receptor 5, μ-opioid receptor, parathyroid hormone 1 receptor and glucagon-like peptide 1 receptor (GLP-1R), highlighting their activation processes upon peptide ligand binding. Comparative analysis of structures bound to endogenous and synthetic peptide ligands reveals critical insights for rational drug design. A case study on GLP-1R demonstrates how structural insights have led to the design of successful drugs for type 2 diabetes and obesity. This comparative structural analysis aims to deepen our understanding of GPCR activation mechanisms and support future drug discovery efforts targeting peptide-binding GPCRs.

Exp. Mol. Med. 2025 Jul;57(7):1467-1481. https://doi.org/10.1038/s12276-025-01497-y
https://pubmed.ncbi.nlm.nih.gov/40629042/