Use of the predictive protein structure algorithm AlphaFold 3 to elucidate the tridimensional structure of the GLP-1 receptor bound to GLP-1 agonists.

Origin: The Tang Prize is awarded on a biennial basis, each with a cash reward of NT$40 million. Projects proposed by the laureates also receive a grant of up to NT$10 million. The 2024 grant for Biopharmaceutical Science is shared between Professor Joel Habener, Professor Svetlana Mojsov, and Professor Jens Juul Holst.

Project Summary: The goal of this research proposal is to apply AlphaFold 3 to determine its ability to predict the 3D structure of the GLP-1 receptor bound to the GLP-1 ligand. The predicted structure will be validated by comparison with the Cryo-EM structure of the GLP-1 receptor in complex with GLP-1 and the G-Alpha protein. This project is a collaboration with Dr. Deena Oren of Deena MX Consulting LLC. A previous collaboration successfully utilized structural mapping to characterize a novel G-protein coupled receptor with dual ligand specificity toward GLP-1 and glucagon, representing the first known example of this receptor class in vertebrates.