title: Mechanism of dimerization of the human melanocortin 1 receptor.
abstract: The melanocortin 1 receptor (MC1R) is a dimeric G protein-coupled receptor expressed in melanocytes, where it regulates the amount and type of melanins produced and determines the tanning response to ultraviolet radiation. We have studied the mechanisms of MC1R dimerization. Normal dimerization of a deleted mutant lacking the seventh transmembrane fragment and the C-terminal cytosolic extension excluded coiled-coil interactions as the basis of dimerization. Conversely, the electrophoretic pattern of wild type receptor and several Cys-->Ala mutants showed that four disulfide bonds are established between the monomers. Disruption of any of these bonds abolished MC1R function, but only the one involving Cys35 was essential for traffic to the plasma membrane. A quadruple Cys35-267-273-275Ala mutant migrating as a monomer in SDS-PAGE in the absence of reducing agents was able to dimerize with WT, suggesting that in addition to disulfide bond formation, dimerization involves non-covalent interactions, likely of domain swap type.
authors.affiliation: Department of Biochemistry and Molecular Biology. School of Medicine, University of Murcia, Campus de Espinardo, 30100-Espinardo, Murcia, Spain.
authors.forename: Paola T
authors.initials: PT
authors.lastname: Zanna
authors.forename: Berta L
authors.initials: BL
authors.lastname: Sánchez-Laorden
authors.forename: Ana B
authors.initials: AB
authors.lastname: Pérez-Oliva
authors.forename: María C
authors.initials: MC
authors.lastname: Turpín
authors.forename: Cecilia
authors.initials: C
authors.lastname: Herraiz
authors.forename: Celia
authors.initials: C
authors.lastname: Jiménez-Cervantes
authors.forename: José C
authors.initials: JC
authors.lastname: García-Borrón
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D044102:Receptor, Melanocortin, Type 1