Submolecular probing of the complement C5a receptor–ligand binding reveals a cooperative two-site binding mechanism

Dumitru et al. probe the ligand-binding mechanism and activation of the human G protein-coupled C5a receptor (C5aR) and discover a cooperativity between the two orthosteric binding sites. Their findings, probing the dynamic aspects of receptor–ligand interaction, are valuable to develop a better understanding of GPCR activation and signalling.