Physics Colloquium – Dr. Qiuyan Chen

Effect of Phosphorylation Barcodes on Arrestin Binding to a Chemokine Receptor

Dr. Qiuyan Chen
Assistant Professor of Biochemistry & Molecular Biology
Indiana University School of Medicine

Cells often fine-tune their responses to signals through chemical tags called phosphorylation ‘barcodes’ placed on receptors at the cell surface. Different G-protein coupled receptor (GPCR) kinases (GRKs) add these barcodes at different sites, but how these patterns influence arrestins — key proteins that control receptor signaling and trafficking — has been unclear.

In this study, we developed a new molecular tool (Fab7) that helps visualize how arrestin2 and arrestin3 interact with a chemokine receptor called ACKR3 when tagged by either GRK2 or GRK5. We found that GRK2 creates more flexible receptor–arrestin assemblies, whereas GRK5 produces more stable ones. Surprisingly, the arrestins interacted more with the surrounding membrane-like environment than with the usual docking pocket of the receptor, and arrestin3 was more dynamic due to a missing membrane anchoring feature. These findings show that both the “barcode pattern” and the arrestin subtype can shape how GPCRs are regulated, which may help explain differences in cellular outcomes such as how efficiently ACKR3 clears chemokines.