The peptide hormone ghrelin binds to membrane-mimetics via its octanoyl chain and an adjacent phenylalanine.

TitleThe peptide hormone ghrelin binds to membrane-mimetics via its octanoyl chain and an adjacent phenylalanine.
Publication TypeJournal Article
Year of Publication2010
AuthorsGrossauer, J., S. Kosol, E. Schrank, and K. Zangger
JournalBioorg Med Chem
Volume18
Issue15
Pagination5483-8
Date Published2010 Aug 1
ISSN1464-3391
KeywordsCell Membrane, Ghrelin, Humans, Nuclear Magnetic Resonance, Biomolecular, Octanes, Phenylalanine, Receptors, Ghrelin, Serine
Abstract

The peptide hormone ghrelin, which is the natural ligand of the membrane-bound growth hormone secretagogue receptor (GHS-R), regulates overall body and cell growth, energy homeostasis, carbohydrate, protein and lipid metabolism and water electrolyte balance. It contains an O-acyl linked octanoyl group on Ser3 and is the only peptide known to contain such a modification. Using solution state NMR spectroscopy and ultrafiltration we found that human ghrelin binds to membrane-mimetic environments via its octanoyl group as well as the aromatic moiety of Phe4. Relaxation enhancements in a paramagnetic environment reveal that both the octanoyl group on Ser3 and the aromatic group on Phe4 are inserted deep into the hydrophobic core of phosphocholine assemblies while the remaining peptide is freely mobile in solution. In contrast, no binding was observed for des-octanoyl ghrelin. Thus, the octanoyl chain, together with the Phe4 aromatic group of ghrelin, functions as a membrane anchor. Our results are in parallel with the previous finding that a bulky hydrophobic group on Ser3 and Phe4 of ghrelin are necessary for its function and thus indicate that membrane-binding is essential for ghrelin function.

DOI10.1016/j.bmc.2010.06.062
Alternate JournalBioorg. Med. Chem.
PubMed ID20621491
PubMed Central IDPMC3038380