Dept. of Biotechnology and Bioinformatics

2026 Spring Semester Seminar

 

2026. 05. 28, 17:00-18:00

산학협력관, 425호

 

Structural Basis of Diversity in GPCR Ligand Recognition and Activation

김진욱

Division of Biological Science & Technology, Yonsei University Mirae Campus, Wonju 26493, Republic of Korea

 

Abstract

G protein-coupled receptors (GPCRs) mediate a wide range of physiological processes by translating diverse extracellular stimuli into specific intracellular responses. This presentation focuses on the structural mechanisms of ligand recognition and activation across distinct GPCR systems characterized by cryo-electron microscopy (cryo-EM). Structural analysis of the neuropeptide Y1 receptor (Y1R) reveals the molecular details of the interactions between the 36-amino acid peptide NPY and Y1R. The extended conformation of the NPY C-terminal segment binds deep into the Y1R transmembrane pocket, and the interactions with extracellular loops explain the importance of the complete N-terminus for Y1R-mediated signaling. In addition, the conformational landscape of complement receptors is defined through the determination of structures in apo, intermediate, and fully active states. These results provide molecular insights into the recognition of both synthetic small-molecule agonists and endogenous ligands, explaining the structural basis for high basal activity. Furthermore, structural insights into Adhesion GPCRs involved in Wnt signaling highlight the unique activation patterns and complexity of these non-canonical receptors. These structural studies provide detailed insights into the diversity of GPCR signaling and its implications for understanding fundamental biological processes. Such structural determinations offer a molecular basis for the rational design of therapeutics targeting specific GPCR-mediated pathways.