title: Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide.
abstract: A model is presented of the melanocortin 1 receptor (MC1R), constructed by use of an unbiased, objective method. The model is created directly from data derived from multiple sequence analysis, a low-resolution EM-projection map of rhodopsin, and the approximate membrane thickness. The model agrees well with available data concerning natural mutations of MC1Rs occurring in different species. A model is also presented of the most rigid ligand for this receptor, the cyclic pentapeptide cHFRWG, shown docked in the receptor model. The receptor-ligand complex model agrees well with available experimental data. The ligand is located between transmembrane region 1 (TM1), TM2, TM3, TM6, and TM7 of the receptor. Multiple interactions occur between ligand and receptor, including interactions with Leu-48 (TM1), Ser-52 (TM1), Glu-55 (TM1), Asn-91 (TM2), Glu-94 (TM2), Thr-95 (TM2) Ile-98 (TM2), Asp-121 (TM3), Thr-124 (TM3), Phe-257 (TM6), Phe-283 (TM7), Asn-290 (TM7), and Asp-294 (TM7) of the receptor.
authors.affiliation: Uppsala University, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Prusis
authors.forename: H B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: R
authors.initials: R
authors.lastname: Muceniece
authors.forename: P
authors.initials: P
authors.lastname: Herzyk
authors.forename: M
authors.initials: M
authors.lastname: Afshar
authors.forename: R E
authors.initials: RE
authors.lastname: Hubbard
authors.forename: J E
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry; D017354:Point Mutation; D011487:Protein Conformation; D018043:Receptors, Corticotropin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044101:Receptors, Melanocortin; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D009074:Melanocyte-Stimulating Hormones