Tyrosine modification enhances metal-ion binding
Journal Title
BIOCHEMICAL JOURNAL
Publication Type
Journal Article
Abstract
Tyrosine sulfation is a common modification of many proteins, and the ability to phosphorylate tyrosine residues is an intrinsic property of many growth-factor receptors. In the present study, we have utilized the peptide hormone CCK8 (cholecystokinin), which occurs naturally in both sulfated and unsulfated forms, as a model to investigate the effect of tyrosine modification on metal-ion binding. The changes in absorbance and fluorescence emission on Fe3+ binding indicated that tyrosine sulfation or phosphorylation increased the stoichiometry from 1 to 2, without greatly affecting the affinity (0.6-2.8 mu M at pH 6.5). Measurement of Ca2+ binding with a Ca2+-selective electrode revealed that phosphorylated CCK8 bound two Ca2+ ions. CCK8 and sulfated CCK8 each bound only one Ca2+ ion with lower affinity. Binding of Ca2+, Zn2+ or Bi3+ to phosphorylated CCK8 did not cause any change in absorbance, but substantially increased the change in absorbance on subsequent addition of Fe3+. The results of the present study demonstrate that tyrosine modification may increase the affinity of metal-ion binding to peptides, and imply that metal ions may directly regulate many signalling pathways.
Publisher
PORTLAND PRESS LTD
Keywords
FERRIC IONS; AGONIST CHOLECYSTOKININ; BIOLOGICAL-ACTIVITY; RECEPTOR; IRON(III); SULFATION; SITE; FLUORESCENCE; SPECTROSCOPY; HYDROLYSIS
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Creation Date: 2008-11-15 12:00:00
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