C-edge loops of arrestin function as a membrane anchor

• Published in: Nature communications 2017-02, Vol.8 (1), p.14258-14258, Article 14258
• Main Authors: Lally, Ciara C M., Bauer, Brian, Selent, Jana, Sommer, Martha E
• Format: Article
• Language: English
• Subjects: 631/45/612/194; 631/57/2266; 82; Amino Acid Sequence; Animals; Arrestins - chemistry; Arrestins - genetics; Arrestins - metabolism; Base Sequence; Binding Sites - genetics; Cattle; Cell Membrane - metabolism; Computational biophysics; Crystal structure; G protein-coupled receptors; Humanities and Social Sciences; Kinases; Molecular Dynamics Simulation; multidisciplinary; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Mutation; Phosphorylation; Protein Binding; Protein Conformation; Proteins; Rhodopsin - chemistry; Rhodopsin - metabolism; Science; Science (multidisciplinary); Signal transduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14258

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. The activity of G-protein-coupled receptors is regulated by their interaction with arrestins. Here the authors show that loops located on C-edge of arrestin-1 serve as a membrane anchor during the multi-step binding process that leads to a stable receptor–arrestin complex.