Copper binding affinity of S100A13, a key component of the FGF-1 nonclassical copper-dependent release complex.

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Sivaraja V, Kumar TK, Rajalingam D, Graziani I, Prudovsky I, Yu C

Copper binding affinity of S100A13, a key component of the FGF-1 nonclassical copper-dependent release complex.

Biophys J. 2006 Sep 1;91(5):1832-43. Epub 2006 Jun 9.

PubMed ID

16766622 [ View in PubMed

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Abstract

S100A13 is a member of the S100 protein family that is involved in the copper-dependent nonclassical secretion of signal peptideless proteins fibroblast growth factor 1 and interleukin 1 lpha. In this study, we investigate the effects of interplay of Cu2+ and Ca2+ on the structure of S100A13 using a variety of biophysical techniques, including multi-dimensional NMR spectroscopy. Results of the isothermal titration calorimetry experiments show that S100A13 can bind independently to both Ca2+ and Cu2+ with almost equal affinity (Kd in the micromolar range). Terbium binding and isothermal titration calorimetry data reveal that two atoms of Cu2+/Ca2+ bind per subunit of S100A13. Results of the thermal denaturation experiments monitored by far-ultraviolet circular dichroism, limited trypsin digestion, and hydrogen-deuterium exchange (using 1H-15N heteronuclear single quantum coherence spectra) reveal that Ca2+ and Cu2+ have opposite effects on the stability of S100A13. Binding of Ca2+ stabilizes the protein, but the stability of the protein is observed to decrease upon binding to Cu2+. 1H-15N chemical shift perturbation experiments indicate that S100A13 can bind simultaneously to both Ca2+ and Cu2+ and the binding of the metal ions is not mutually exclusive. The results of this study suggest that the Cu2+-binding affinity of S100A13 is important for the formation of the FGF-1 homodimer and the subsequent secretion of the signal peptideless growth factor through the nonclassical release pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Calcium	Protein S100-A13	Protein	Humans	Unknown	Not Available	Details
Calcium chloride	Protein S100-A13	Protein	Humans	Unknown	Not Available	Details