Chimeric melanocortin MC1 and MC3 receptors: identification of domains participating in binding of melanocyte-stimulating hormone peptides.
The melanocortin receptors MC1 and MC3 are G protein-coupled receptors that have substantial structural similarities and bind melanocyte peptides but with different affinity profiles. We constructed a series of chimeric MC1/MC3 receptors to identify the epitopes that determine their selectivities for natural melanocyte peptides and synthetic analogues. The chimeric constructs were made by a polymerase chain reaction that used identical regions in or just outside transmembranes (TM) 1, 4, and 6 and divided the receptors into four segments. Saturation and competition studies on the expressed chimeric proteins indicate that TM1, TM2, TM3, and TM7 are involved in the subtype-specific binding of melanocyte peptides to these receptors. The results support the hypothesis that TM4 and TM5 may not contribute to the ligand-binding specificity of the MC receptors. This is the first report to describe the subtype-specific hormone-binding domains of the melanocortin receptor family.
Schiöth
H B
HB
Department of Pharmaceutical Pharmacology, Uppsala University, Uppsala, Sweden.
Yook
P
P
Muceniece
R
R
Wikberg
J E
JE
Szardenings
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D001667:Binding, Competitive; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000378:metabolism*; D044101:Receptors, Melanocortin; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D016415:Sequence Alignment
D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011993:Recombinant Fusion Proteins; D009074:Melanocyte-Stimulating Hormones