The structure basis of arrestin mediated GPCR signaling

Abstract

Arrestin selectively binds the phosphorylated active receptor to either terminate the G protein dependent signaling or initiate G protein independent signaling. Receptor binding induces global conformational changes in arrestin and allosterically activates the region for downstream effectors binding. My research is focused on elucidating the structural basis of arrestin signaling. In particular, I am trying to answer the following questions: 1. What is the conformation of arrestin in the active form? 2. How does arrestin activate downstream signaling? 3. How is the receptor activation allosterically linked to the effector binding in arrestin? I have used NMR, EPR, crystallography and various techniques to look at arrestin dynamics and have determined the structure of active arrestin-3. Collectively, my results revealed the high dynamic of arrestin and identified key elements for receptor and downstream effector binding.