Araç Lab captures images of aGPCR and proposes a new way of activation

Insights of the study enlighten further research and handling of adhesion G protein-coupled receptor

One of the Center for Mechanical Excitability’s collaborators, the Araç lab, has recently achieved a major milestone: capturing the first full structural images of an adhesion G protein-coupled receptor (aGPCR), specifically Latrophilin3. These receptors are key in helping cells adhere to each other to generate signals inside the body. When not functioning well, they can play a central role in the development of brain disorders, cancer, and growth issues.

The team engineered a synthetic antibody to stabilize Latrophilin3’s GAIN domain, enabling them to freeze and image its complete architecture. Further analysis with FRET confirmed that the receptor’s extracellular domain shifts between multiple orientations, suggesting an adjustable mechanism for signal modulation rather than a simple on and off switch.

Read more at: https://biologicalsciences.uchicago.edu/news/agpcr-first-complete-images 

Publication: Kordon, S.P., Cechova, K., Bandekar, S.J. et al. Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function. Nat Commun 15, 10545 (2024). https://doi.org/10.1038/s41467-024-54836-4