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.
Svendsen
Angela Manegold
AM
Receptor Systems Biology Laboratory, Hagedorn Research Institute, Gentofte, Denmark. agms@hagedorn.dk
Vrecl
Milka
M
Knudsen
Louise
L
Heding
Anders
A
Wade
John D
JD
Bathgate
Ross A D
RA
De Meyts
Pierre
P
Nøhr
Jane
J
D006801:Humans; D007328:Insulin / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D018000:Receptors, Peptide / Q000737:chemistry / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism
D007328:Insulin; C417543:RXFP1 protein, human; C472867:RXFP2 protein, human; C410092:RXFP3 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin