title: Structural mechanism of GPCR-arrestin interaction: recent breakthroughs.
abstract: G protein-coupled receptors (GPCRs) are a major membrane receptor family with important physiological and pathological functions. In the classical signaling pathway, ligand-activated GPCRs couple to G proteins, thereby inducing G protein-dependent signaling pathways and phosphorylation by G protein-coupled receptor kinases (GRKs). This leads to an interaction with arrestins, which results in GPCR desensitization. Recently, non-classical GPCR signaling pathways, mediated by GPCR-bound arrestins, have been identified. Consequently, arrestins play important roles in GPCR signaling not only with respect to desensitization but also in relation to G protein-independent signal transduction. These findings have led to efforts to develop functionally biased (i.e. signal transduction biased) GPCR-targeting drugs. One of these efforts is aimed at understanding the structural mechanism of functionally biased GPCR signaling, which includes understanding the G protein-selectivity or arrestin-selectivity of GPCRs. This goal has not yet been achieved; however, great progress has been made during the last 3 years toward understanding the structural mechanism of GPCR-mediated arrestin activation. This review will discuss the recent breakthroughs in the conformational understanding of GPCR-arrestin interaction.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 440746, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 440746, Republic of Korea.
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 440746, Republic of Korea.
authors.forename: Hee Ryung
authors.initials: HR
authors.lastname: Kim
authors.affiliation: College of Pharmacy & Department of Molecular Science and Technology, Ajou University, Suwon, 443721, Republic of Korea.
authors.forename: Min-Duk
authors.initials: MD
authors.lastname: Seo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 440746, Republic of Korea. kychung2@skku.edu.
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Chung
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D015394:Molecular Structure; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019390:Arrestins; D043562:Receptors, G-Protein-Coupled
keywords: Arrestin; GPCR; Structure