Proadrenomedullin N-terminal peptide and cortistatin activation of MrgX2 receptor is based on a common structural motif.

The G protein-coupled receptor MrgX2 belongs to the large family of the Mas-related genes or sensory neuron-specific G protein-coupled receptors. The MrgX2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin N-terminal peptides (PAMP). Here we investigated the structure activity relationship of PAMP and identified key structural features that are shared with cortistatin and might explain why two apparently unrelated peptides are able to activate a single G protein-coupled receptor.