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

• Published in: Nature communications 2014-09, Vol.5 (1), p.4801-4801, Article 4801
• Main Authors: Szczepek, Michal, Beyrière, Florent, Hofmann, Klaus Peter, Elgeti, Matthias, Kazmin, Roman, Rose, Alexander, Bartl, Franz J., von Stetten, David, Heck, Martin, Sommer, Martha E., Hildebrand, Peter W., Scheerer, Patrick
• Format: Article
• Language: English
• Subjects: 631/45/535; 82/80; 96; 96/95; Amino Acid Motifs; Animals; Arrestins - metabolism; Binding, Competitive; Cattle; Crystallography, X-Ray; Humanities and Social Sciences; Life Sciences; Models, Molecular; multidisciplinary; Protein Structure, Tertiary; Receptors, G-Protein-Coupled - metabolism; Rhodopsin - metabolism; Science; Science (multidisciplinary); Signal Transduction; Spectroscopy, Fourier Transform Infrared; X-Ray Absorption Spectroscopy
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5801

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 G i /G t 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. G-protein-coupled receptors (GPCRs) transmit signals through intracellular heterotrimeric G proteins and arrestins. Here, Szczepek et al. present the structure of a common binding interface for Gα and arrestin on rhodopsin to shed light on key interactions that mediate transduction of specific signals through a single GPCR.