"The adipokine chemerin is the endogenous ligand of the chemokine-like receptor 1 (CMKLR1), a member of the family of G protein-coupled receptors (GPCR). This protein ligand plays an important role in obesity and inflammatory processes. Stable receptor-ligand interactions are highly relevant for its different physiological effects, e. g. the migration of immune cells towards sites of inflammation. Here, we demonstrate that negative charges in the CMKLR1 N-terminus are involved in the formation of strong contacts with a specific positively charged patch at the surface of full-length chemerin, which is absent in the short nonapeptide agonist chemerin-9 explaining its reduced affinity. Using receptor chimera of G protein-coupled receptor 1 (GPR1) and CMKLR1, we were able to identify the residues of this interaction and its relevance for stable full-length chemerin binding. This may help to develop more potent ligands for the treatment of inflammatory related diseases."