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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 26; no. 5; pp. 779 - 789
• Main Authors: Thuau, Romain, Guilhaudis, Laure, Ségalas-Milazzo, Isabelle, Chartrel, Nicolas, Oulyadi, Hassan, Boivin, Stéphane, Fournier, Alain, Leprince, Jérôme, Davoust, Daniel, Vaudry, Hubert
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2005; Elsevier Science; Elsevier
• Subjects: 1H NMR; Amino Acid Sequence; Biological and medical sciences; Cell Behavior; Cellular Biology; Chemical Sciences; Circular Dichroism; Fundamental and applied biological sciences. Psychology; Humans; Life Sciences; Magnetic Resonance Spectroscopy; Medicinal Chemistry; Methanol; Methanol - chemistry; Molecular modeling; Molecular Sequence Data; Nerve Tissue Proteins; Nerve Tissue Proteins - chemistry; Neurobiology; Neurons and Cognition; Neuropeptide; Neuropeptides; Pharmaceutical sciences; Pharmacology; Protein Structure, Secondary; RFamide-related peptide; Solution structure; Vertebrates: endocrinology; CD; SDS; NOE; HMBC; 1H NMR; RMSD; TOCSY; COSY; RFamide-related peptide; Neuropeptide; TPPI; Solution structure; Molecular modeling; Fmoc; NOESY; HSQC; MALDI/TOF-MS; Human; Peptides
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2005.01.006

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 α-helical structure (Pro 4–Arg 17), 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.