Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity

Romain Thuau (1, 2) , Laure Guilhaudis (1, 2) , Isabelle Ségalas-Milazzo (1, 2) , Nicolas Chartrel (3, 2) , Hassan Oulyadi (1, 2) , Stéphane Boivin (1, 2, 4) , Alain Fournier (4) , Jérôme Leprince (3, 2) , Daniel Davoust (1, 2) , Hubert Vaudry (3, 2)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
3 Neuroendocrinologie cellulaire et moléculaire
4 INRS-IAF - Institut Armand Frappier

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.

Domaines: Chimie thérapeutique; Interactions cellulaires [q-bio.CB]; Neurobiologie; Pharmacologie

Romain Thuau, Laure Guilhaudis, Isabelle Ségalas-Milazzo, Nicolas Chartrel, Hassan Oulyadi, et al.. Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity. Peptides, 2005, 26 (5), pp.779-789. ⟨10.1016/j.peptides.2005.01.006⟩. ⟨hal-01974257⟩