Almost 35% of drugs approved by the Food and Drug Administration work by targeting G protein-coupled receptors (GPCRs), proteins embedded in cell membranes that allow cells to communicate with each other. Adhesion G protein-coupled receptors (aGPCRs) are the second largest family of these receptors in humans. As their name suggests, they help cells adhere, or stick to each other, and send signals inside the body.
These receptors are involved in many processes, such as how tissues grow, how the immune system works, and how organs form. Problems with aGPCRs can also lead to diseases like cancer, brain disorders, and growth issues. Despite the obviously important role they play in the body, however, there are no drugs approved to target aGPCRs because they are large, complex, and difficult to study.
New research from the University of Chicago combines two powerful imaging techniques to study the complete structure of a common aGPCR, including how its long and complex extracellular region interacts with the transmembrane region embedded in the cell surface. The different positions and movements of the extracellular region appear to be an important way to activate the receptor.
This opens up new opportunities for drugging adhesion GPCRs, because now we are showing that the extracellular region is communicating with the transmembrane region.”
Demet Araç, PhD, Associate Professor of Biochemistry and Molecular Biology at UChicago and senior author of the new study
The results were published this month in Nature Communications.
Capturing new images and new configurations
The extracellular region