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

G-protein-coupled receptors (GPCRs) transmit extracellular signals to activate intracellular heterotrimeric G proteins (G alpha beta gamma) and arrestins. For G protein signalling, the G alpha C-terminus (G alpha CT) binds to a cytoplasmic crevice of the receptor that opens upon activation. A consensus motif is shared among GaCT from the G(i)/G(t) family and the 'finger loop' region (ArrFL1-4) of all four arrestins. Here we present a 2.75 angstrom crystal structure ofrrFL-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 GaCT 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.