title: An investigation into the origin of the biased agonism associated with the urotensin II receptor activation.
abstract: The urotensin II receptor (UTR) has long been studied mainly for its involvement in the cardiovascular homeostasis both in health and disease state. Two endogenous ligands activate UTR, i.e. urotensin II (U-II) and urotensin II-related peptide (URP). Extensive expression of the two ligands uncovers the diversified pathophysiological effects mediated by the urotensinergic system such as cardiovascular disorders, smooth muscle cell proliferation, renal disease, diabetes, and tumour growth. As newly reported, U-II and URP have distinct effects on transcriptional activity, cell proliferation, and myocardial contractile activities supporting the idea that U-II and URP interact with UTR in a distinct manner (biased agonism). To shed light on the origin of the divergent activities of the two endogenous ligands, we performed a conformational study on URP by solution NMR in sodium dodecyl sulfate micelle solution and compared the obtained NMR structure of URP with that of hU-II previously determined. Finally, we undertook docking studies between URP, hU-II, and an UT receptor model.
authors.affiliation: Department of Pharmacy, University of Naples 'Federico II', I-80131, Naples, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Merlino
authors.forename: Antonio
authors.initials: A
authors.lastname: Limatola
authors.forename: Ali Munaim
authors.initials: AM
authors.lastname: Yousif
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D036361:Peptide Hormones / Q000819:agonists* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013329:Structure-Activity Relationship; D014579:Urotensins / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; C479080:UTS2B protein, human; C121697:UTS2R protein, human; D014579:Urotensins; D012967:Sodium Dodecyl Sulfate; C029677:urotensin II
keywords: biased agonism; conformation by NMR; docking studies; therapeutic peptide; urotensin II-related peptide; urotensin-II