The melanocortin-1 receptor carboxyl terminal pentapeptide is essential for MC1R function and expression on the cell surface.
The pigmentary actions of the melanocortins are mediated by the melanocortin-1 receptor (MC1R), a seven transmembrane domains receptor positively coupled to Gs and the cAMP cascade. In order to define the structure-function relationships of potentially relevant domains in MC1R, particularly its C-terminal cytosolic tail, we generated and analyzed several variants with C-terminal deletions, as well as point mutants in selected residues of the human MC1R. We show that the MC1R C-terminal pentapeptide is essential for proper receptor expression on the plasma membrane, and that residues Thr314, Cys315 and Trp317 are at least partially responsible for this effect.
Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Apto 4021, 30100 Espinardo, Murcia, Spain.
J
J
Sánchez-Más
B L
BL
Sánchez-Laorden
L A
LA
Guillo
C
C
Jiménez-Cervantes
J C
JC
García-Borrón
D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000502:physiology*; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D014162:Transfection
D009842:Oligopeptides; D044102:Receptor, Melanocortin, Type 1; D003545:Cysteine; D000409:Alanine