RT Journal Article
SR Electronic
T1 Chimeric Melanocortin MC1 and MC3 Receptors: Identification of Domains Participating in Binding of Melanocyte-Stimulating Hormone Peptides
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 154
OP 161
DO 10.1124/mol.54.1.154
VO 54
IS 1
A1 Schiöth, Helgi B.
A1 Yook, Philip
A1 Muceniece, Ruta
A1 Wikberg, Jarl E. S.
A1 Szardenings, Michael
YR 1998
UL http://molpharm.aspetjournals.org/content/54/1/154.abstract
AB 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.