Sex peptides and MIPs can activate the same G protein-coupled receptor

► Sex peptide receptor is activated by MIPs as well as sex peptide. ► MIPs likely are sex peptide receptor's ancestral ligands. ► Characteristic Trp residues in MIPs and sex peptide are key in activating sex peptide receptor. ► A chimeric peptide, based on MIP and sex peptide, is a potent agonist of sex peptide receptor.