title: Conformational features of human melanin-concentrating hormone: an NMR and computational analysis.
abstract: The conformational features of human melanin-concentrating hormone (hMCH) [Asp1-Phe2-Asp3-Met4-Leu5-Arg6-cyclo(S[bond]S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13-Arg14-Pro15-Cys16)-Trp17-Gln18-Val19], in water and in a CD(3)CN/H(2)O (1:1 v/v) mixture at 298 K, have been determined by NMR spectroscopy followed by simulated annealing and molecular dynamics analyses to identify conformer populations. Backbone clustering analysis of NMR-spectroscopy-derived structures in the 7-16 peptide region led to the identification of a single representative structure in each solvent. Both root mean square deviation clustering and secondary structure analysis of the final conformers in both solvents show substantial convergence of most conformers into a single fold in the 4-17 region, with a limited variability around Gly10 and Tyr13 on going from CD(3)CN/H(2)O to pure water. The main feature deduced from the analysis of secondary structures is the occurrence of an N-terminal alpha helix of variable length, which spans an overall residue range of 2-9. A comparative analysis in the two solvents highlights that these structures are substantially different from that reported in the literature for the cyclic MCH(5-14) subunit of salmon MCH, which was used to perform a molecular characterization of the MCH/receptor complex. Our conformational data call for a critical revision of the proposed MCH/receptor complex model.
authors.affiliation: Dipartimento di Scienze Ambientali, Seconda Università di Napoli via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Vitale
authors.forename: Laura
authors.initials: L
authors.lastname: Zaccaro
authors.forename: Benedetto
authors.initials: B
authors.lastname: Di Blasio
authors.forename: Roberto
authors.initials: R
authors.lastname: Fattorusso
authors.forename: Carla
authors.initials: C
authors.lastname: Isernia
authors.forename: Pietro
authors.initials: P
authors.lastname: Amodeo
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019295:Computational Biology; D006801:Humans; D006860:Hydrogen Bonding; D007028:Hypothalamic Hormones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008543:Melanins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010907:Pituitary Hormones / Q000737:chemistry*; D011487:Protein Conformation; D012997:Solvents
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D012997:Solvents; C019463:melanin-concentrating hormone