Fig. 8 | Nature Communications

Fig. 8

From: Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation

Fig. 8

Phosphorylation motifs within the larger family of GPCRs. a The three functionally distinct phosphorylation motifs described in this study are illustrated on aligned C-termini from two class B GPCRs. Negatively charged amino acids are colored blue and potential phosphorylation sites are colored yellow. b Crystal structure of the fully phosphorylated C-terminus of the class B GPCR V2 vasopressin receptor (V2Rpp, green stick model with phosphorylation sites highlighted in red) bound to arrestin-2 (gray surface model) (PDB accession 4JQI)37. Important interactions between certain phosphate groups on the peptide (red) and basic residues on arrestin-2 (blue patches) are indicated (see main text for details). c Sequence alignments of receptor C-termini from class A and class B GPCRs. All serines and threonines (possible sites of phosphorylation by the GPCR kinases) are highlighted in yellow. Negatively charged residues are highlighted in blue. The sequences are aligned based on the key site motif (serine or threonine residues separated by two amino acids, green box) and the negatively charged motif (two acidic or one phosphorylatable serine or threonine residues 8 residues upstream of the closest activator site, blue box). The alignment indicates that all class B receptors (strong arrestin binders) contain both the key sites and the negatively charged motif. In contrast, class A receptors (weak arrestin binders) generally lack the negatively charged motif (see Supplementary Note 1 for a more detailed description)