Bones are one of the few organs in which uranyl (UO2(2+)) accumulates. This 
large dioxo-cation displays affinity for carboxylates, phenolates and 
phosphorylated functional groups in proteins. The noncollagenous protein 
osteopontin (OPN) plays an important role in bone homeostasis. It is mainly 
found in the extracellular matrix of mineralized tissues but also in body fluids 
such as milk, blood and urine. Furthermore, OPN is an intrinsically disordered 
protein, which, like other proteins of the SIBLING family, contains a 
polyaspartic acid sequence and numerous patterns of alternating acidic and 
phosphorylated residues. All these properties led to the hypothesis that this 
protein could be prone to UO2(2+) binding. In this work, a simple purification 
procedure enabling highly purified bovine (bOPN) and human OPN (hOPN) to be 
obtained was developed. Various biophysical approaches were set up to study the 
impact of phosphorylations on the affinity of OPN for UO2(2+) as well as the 
formation of stable complexes originating from structural changes induced by the 
binding of this metal cation. The results obtained suggest a new mechanism of 
the interaction of UO2(2+) with bone metabolism and a new role for OPN as a 
metal transporter.