Use of 19F NMR to probe conformational changes of arrestin-3

Abstract

In addition to their canonical function as negative regulators of G protein coupled receptors (GPCRs), arrestins, a small family of cyclic protein, serve as multi-functional adaptors by tethering several signaling components together. To elicit the appropriate cellular response, arrestins have to ensure that the right components are linked together to prevent the formation of mismatched protein complexes. In addition to more than 700 GPCRs, two non-visual arrestins can interact with dozens other protein partners. Thus, the recruitments of the signal effector proteins to arrestin should be precisely regulated. We hypothesize that binding induced conformational changes play decisive roles in regulating the recruitments of binding partners to arrestins. It is now clear that arrestin goes significant conformational movements in many regulating process. To exploit the arrestin-mediated signaling as adaptors, the structural basis of protein-protein interactions between arrestin and non-receptor binding partners is essential. The broad objective of this proposal is to explore the binding-induced conformational changes of arrestins by signaling effector proteins. The primary goal of this current proposal is developing a 19F-NMR method to detect the local movements of arrestin protein.