Arrestins desensitize G protein-coupled receptors (GPCRs) and act as mediators
of signalling. Here we investigated the interactions of arrestin-1 with two
functionally distinct forms of the dim-light photoreceptor rhodopsin. Using
unbiased scanning mutagenesis we probed the individual contribution of each
arrestin residue to the interaction with the phosphorylated apo-receptor
(Ops-P) and the agonist-bound form (Meta II-P). Disruption of the polar core
or displacement of the C-tail strengthened binding to both receptor forms. In
contrast, mutations of phosphate-binding residues (phosphosensors) suggest the
phosphorylated receptor C-terminus binds arrestin differently for Meta II-P
and Ops-P. Likewise, mutations within the inter-domain interface, variations
in the receptor-binding loops and the C-edge of arrestin reveal different
binding modes. In summary, our results indicate that arrestin-1 binding to
Meta II-P and Ops-P is similarly dependent on arrestin activation, although
the complexes formed with these two receptor forms are structurally distinct
