Many faces of the GPCR-arrestin interaction
| Autor: | Kiae Kim, Ka Young Chung |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Protein Conformation
alpha-Helical 0301 basic medicine Arrestins MAP Kinase Signaling System G protein media_common.quotation_subject Crystallography X-Ray Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Drug Discovery Arrestin Animals Humans Phosphorylation Internalization G protein-coupled receptor media_common G protein-coupled receptor kinase Chemistry Kinase Organic Chemistry G-Protein-Coupled Receptor Kinases Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine Protein Conformation beta-Strand Signal transduction hormones hormone substitutes and hormone antagonists |
| Zdroj: | Archives of Pharmacal Research. 43:890-899 |
| ISSN: | 1976-3786 0253-6269 |
| DOI: | 10.1007/s12272-020-01263-w |
| Popis: | G protein-coupled receptors (GPCRs) belong to a major receptor family and regulate important physiological and pathological functions. Upon agonist activation, GPCRs couple to G proteins and induce the activation of G protein-dependent signaling pathways. The agonist-activated GPCRs are also phosphorylated by G protein-coupled receptor kinases (GRKs), which promote their interaction with arrestins. Arrestin binding induces desensitization (i.e., inability to couple to G proteins) and/or internalization of GPCRs. Arrestins not only desensitize and/or internalize GPCRs but also mediate other downstream signals such as mitogen-activated protein kinases. G protein-mediated signaling and arrestin-mediated signaling often result in different functional outcomes, and therefore, it has been suggested that signaling-selective regulation of GPCRs could lead to the development of more effective treatments with fewer side effects. Thus, studies have attempted to develop functionally biased (i.e., signaling-selective) GPCR-targeting drugs. To this end, it is important to elucidate the structural mechanism underlying functionally biased GPCR signaling, which includes understanding the structural mechanism underlying the GPCR-arrestin interaction. This review aims discuss the structural aspects of the GPCR-arrestin interaction, focusing on the differences between reported GPCR-arrestin complex structures. |
| Databáze: | OpenAIRE |
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