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KMID : 0043320200430090890
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Archives of Pharmacal Research
2020 Volume.43 No. 9 p.890 ~ p.899
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Many faces of the GPCR-arrestin interaction
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Kim Ki-Ae
Chung Ka-Young
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Abstract
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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.
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KEYWORD
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Arrestin, Structure, GPCR
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