Related Experiment Video

Updated: Feb 9, 2026

G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay
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G Protein-selective GPCR Conformations Measured Using FRET Sensors in a Live Cell Suspension Fluorometer Assay

Published on: September 10, 2016

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Molecular mechanism of modulating arrestin conformation by GPCR phosphorylation

Andrija Sente1, Raphael Peer2, Ashish Srivastava3

  • 1MRC Laboratory of Molecular Biology, Cambridge, UK. as2475@cam.ac.uk.

Nature Structural & Molecular Biology
|June 7, 2018
PubMed

Insights

Arrestins control G-protein-coupled receptor (GPCR) signaling. This study reveals how GPCR phosphorylation patterns dictate arrestin conformations, influencing signaling outcomes and providing a new model for arrestin activation.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Arrestins regulate signaling for phosphorylated G-protein-coupled receptors (GPCRs).
  • Specific receptor phosphorylation patterns (barcodes) dictate arrestin conformations, affecting desensitization, internalization, and signaling.
  • The precise mechanisms of arrestin activation and how phosphorylation patterns induce conformational changes remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of arrestin activation.
  • To understand how distinct GPCR phosphorylation patterns induce specific arrestin conformational changes.

Main Methods:

  • Analysis of individual arrestin amino acid contributions to conformational states.
  • Identification of conserved structural motifs and their role in arrestin conformation.

Main Results:

  • A conserved motif restricting finger loop mobility in inactive arrestin was identified, modulated by receptor phosphorylation.
  • Distinct arrestin structural motifs ('micro-locks') interact selectively with proximal and distal receptor phosphorylation sites.
  • These interactions induce specific arrestin conformations.

Conclusions:

  • A model is proposed where GPCR C-terminal phosphorylation patterns combinatorially modulate arrestin conformations.
  • This modulation affects the finger loop and other phosphorylation-sensitive elements, driving distinct functional outcomes.
  • This provides a framework for understanding how arrestin activation is regulated by GPCR phosphorylation.

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