Dimerization and Negative Cooperativity in the Relaxin Family Peptide Receptors

Peptides of the relaxin family bind to the relaxin family peptide receptors or RXFPs, members of the G-protein-coupled receptor (GPCR) superfamily. For many years, ligand binding to GPCRs was thought to take place as monomeric complexes, ignoring early evidence of negative cooperativity. However, recent research has shown that most GPCRs form constitutive dimers or larger oligomers. The connection between dimerization and negative cooperativity has now been shown for several GPCRs, including the thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone receptors, which like RXFP1 and -2 belong to the leucine-rich repeat-containing subgroup of class A GPCRs. We recently demonstrated homodimerization and negative cooperativity for RXFP1 and RXFP2 as well as their heterodimerization. Another study showed that RXFP1 has to homodimerize in order to be transported from the endoplasmic reticulum to the cell membrane.