Please use this identifier to cite or link to this item:
Title: Ferric ions are essential for the biological activity of the hormone glycine-extended gastrin.
Austin Authors: Pannequin, Julie;Barnham, Kevin J;Hollande, Frederic;Shulkes, Arthur;Norton, Raymond S;Baldwin, Graham S
Affiliation: University of Melbourne Department of Surgery, Austin Campus, ARMC, Heidelberg, Victoria 3084, Australia
Issue Date: 20-Sep-2002
Publication information: The Journal of Biological Chemistry 2002; 277(50): 48602-9
Abstract: Amidated and nonamidated gastrins elicit different biological effects via distinct receptors in different tissues. Amidated gastrin 17 stimulates gastric acid secretion and the development of gastric carcinoids, whereas glycine-extended gastrin 17 stimulates proliferation of the colonic mucosa and the development of colorectal cancers. Because glycine-extended gastrin 17 binds two ferric ions with high affinity (Baldwin, G. S., Curtain, C. C., and Sawyer, W. H. (2001) Biochemistry 40, 10741-10746), we have investigated the identity of the iron ligands and the role of ferric ions in biological activity. Here we report the solution structure of glycine-extended gastrin 17, determined by NMR spectroscopy. The spectral changes observed upon the addition of ferric ions revealed that Glu(7) acted as a ligand at the first ferric binding site, and that Glu(8) and Glu(9) acted as ligands at the second ferric ion binding site. Fluorescence quenching experiments confirmed that a GglyE7A mutant bound only one ferric ion. The inability of this mutant to stimulate proliferation or migration in the IMGE-5 cell line and the observation that the iron chelator desferrioxamine selectively blocked the effects of glycine-extended gastrin 17 indicated that binding of a ferric ion to Glu(7) was essential for biological activity. This is the first report of an essential role for a metal ion in the action of a hormone.
Gov't Doc #: 12270941
DOI: 10.1074/jbc.M208440200
Type: Journal Article
Subjects: Amino Acid Sequence
Cell Line
Ferric Compounds.chemistry
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Protein Conformation
Sequence Homology, Amino Acid
Spectrometry, Fluorescence
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Nov 30, 2022

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.