Crystal structure of a common GPCR-binding interface for G protein and arrestin

Nat Commun. 2014 Sep 10:5:4801. doi: 10.1038/ncomms5801.

Abstract

G-protein-coupled receptors (GPCRs) transmit extracellular signals to activate intracellular heterotrimeric G proteins (Gαβγ) and arrestins. For G protein signalling, the Gα C-terminus (GαCT) binds to a cytoplasmic crevice of the receptor that opens upon activation. A consensus motif is shared among GαCT from the Gi/Gt family and the 'finger loop' region (ArrFL1-4) of all four arrestins. Here we present a 2.75 Å crystal structure of ArrFL-1, a peptide analogue of the finger loop of rod photoreceptor arrestin, in complex with the prototypical GPCR rhodopsin. Functional binding of ArrFL to the receptor was confirmed by ultraviolet-visible absorption spectroscopy, competitive binding assays and Fourier transform infrared spectroscopy. For both GαCT and ArrFL, binding to the receptor crevice induces a similar reverse turn structure, although significant structural differences are seen at the rim of the binding crevice. Our results reflect both the common receptor-binding interface and the divergent biological functions of G proteins and arrestins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Arrestins / metabolism*
  • Binding, Competitive*
  • Cattle
  • Crystallography, X-Ray
  • Models, Molecular
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / metabolism*
  • Rhodopsin / metabolism
  • Signal Transduction
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Absorption Spectroscopy

Substances

  • Arrestins
  • Receptors, G-Protein-Coupled
  • Rhodopsin

Associated data

  • PDB/4PXF