C-edge loops of arrestin function as a membrane anchor

Lally, Ciara C.M.; Bauer, Brain; Selent, Jana; Sommer, Martha E.

doi:http://dx.doi.org/10.1038/ncomms14258

C-edge loops of arrestin function as a membrane anchor

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Lally CCM, Bauer B, Selent J, Sommer ME. C-edge loops of arrestin function as a membrane anchor. Nature Communications. 2017;8:14258. DOI: 10.1038/ncomms14258

Abstract

G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin–receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane, and we show that these interactions are distinct in the pre-complex and high-affinity complex in regard to their conformation and orientation. Our results expand current knowledge of C-edge structure and further illuminate the conformational transitions that occur in arrestin along the pathway to tight receptor binding.