The Arrestin-Receptor Complex: Exciting Answers and New Questions
To better understand the molecular mechanism of arrestin-mediated signaling, detailed structural information on the arrestin-receptor complex is necessary. Biochemical studies provided some information about how arrestins are recruited by active receptors. The X-ray laser crystal structure of the rhodopsin–arrestin complex reveals unique structural features, which include the asymmetric binding of arrestin to rhodopsin. Arrestin adopts the active conformation, with a ~20° rotation between the N- and C-domains of the molecule, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. Rhodopsin–arrestin complex gives important insights into how G protein–coupled receptor signaling is terminated by arrestin and reveals structural basis of the mechanism of arrestin-biased signaling.
KeywordsCrystal structure GPCR Rhodopsin Arrestin Biased signaling
- Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJ, Gurevich VV, Chen J, Rieke F (2015) C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. Elife 4:eLife.05981. doi: 10.7554/eLife.05981 CrossRefGoogle Scholar
- Karaki S, Becamel C, Murat S, Mannoury la Cour C, Millan MJ, Prezeau L, Bockaert J, Marin P, Vandermoere F (2014) Quantitative phosphoproteomics unravels biased phosphorylation of serotonin 2A receptor at Ser280 by hallucinogenic versus nonhallucinogenic agonists. Mol Cell Proteomics 13:1273–1285CrossRefPubMedPubMedCentralGoogle Scholar
- Nobles KN, Xiao K, Ahn S, Shukla AK, Lam CM, Rajagopal S, Strachan RT, Huang TY, Bressler EA, Hara MR et al (2011) Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin. Sci Signal 4:ra51CrossRefPubMedPubMedCentralGoogle Scholar