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Updated: Mar 1, 2026

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
Published on: June 28, 2019
Understanding the GPCR biased signaling through G protein and arrestin complex structures
X Edward Zhou1, Karsten Melcher1, H Eric Xu1
1Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, USA.
Abstract:
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and are important drug targets for many human diseases. The determination of the 3-D structure of GPCRs and their signaling complexes has promoted our understanding of GPCR biology and provided templates for structure-based drug discovery. In this review, we focus on the recent structure work on GPCR signaling complexes, the β2-adrenoreceptor-Gs and the rhodopsin-arrestin complexes in particular, and highlight the structural features of GPCR complexes involved in G protein- and arrestin-mediated signal transduction. The crystal structures reveal distinct structural mechanisms by which GPCRs recruit a G protein and an arrestin. A comparison of the two complex structures provides insight into the molecular mechanism of functionally selective GPCR signaling, and a structural basis for the discovery of G protein- and arrestin-biased treatments of human diseases related to GPCR signal transduction.
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