Fig. 3: AlphaFold2 models of apelin and ELA bound apelin receptor provide a structural rationale for altered binding at the T/M892.64 and R/H1684.64 variants.

a Cartoon representation of the overall model of human apelin receptor (wheat) bound to mini-Gi (blue). Amino acid positions for variants identified in individuals recruited to the 100,000 Genomes Project are represented as spheres: V38^1.42 (blue), T89^2.64 (red), R168^4.64 (magenta), G45^1.49 and T227^5.64 (yellow), and six others not experimentally characterised (green). The C-termini of apelin (cyan) and ELA (orange) peptides are shown as sticks. b Close-up views of apelin (left, cyan) and ELA (right, orange) peptide show C-termini binding in the orthosteric site of the human apelin receptor. Side chains of residues lining the peptide binding pocket, notably R1684.64 interacting with the C-terminal carboxyl group of the peptides, and the modelled T/M89^2.64 substitution impacting binding of ELA (steric clash indicated by red polygon) but not that of apelin, are represented as sticks. Source data are provided as a Source Data File for 3b.