title: Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity.
abstract: A novel hypothalamic neuropeptide of the RFamide family, comprising 26 amino acids residues and thus termed 26RFa, has been recently characterized in human, and was found to be the endogenous ligand for the orphan G protein-coupled receptor GPR103. Intracerebroventricular injection of 26RFa provokes a robust increase in food intake in rodents. In the present study, we have investigated the solution conformation of 26RFa by using two-dimensional NMR spectroscopy in different media. In water, 26RFa exhibits mainly a random coil conformation although the presence of a nascent helix was detected between residues 6 and 15. In methanol, 26RFa adopts a well-defined conformation consisting of an amphipathic alpha-helical structure (Pro4-Arg17), flanked by two N- and C-terminal disordered regions. The strong conservation, from amphibians to mammals, of the amino acid sequence corresponding to the amphipathic helix and to the C-terminal flexible octapeptide of 26RFa, suggests that these two domains are crucial for the interaction of the peptide with its receptor.
authors.affiliation: Laboratory of Nuclear Magnetic Resonance, European Institute for Peptide Research (IFRMP 23), UMR 6014 CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Thuau
authors.forename: Laure
authors.initials: L
authors.lastname: Guilhaudis
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ségalas-Milazzo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.forename: Hassan
authors.initials: H
authors.lastname: Oulyadi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Boivin
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Daniel
authors.initials: D
authors.lastname: Davoust
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009479:Neuropeptides; D017433:Protein Structure, Secondary
chemical_list: D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C480638:prepro-26RFa protein, human; D000432:Methanol