A Shielding Topology Stabilizes the Early Stage Protein-Mineral Complexes of Fetuin-A and Calcium Phosphate: A Time-Resolved Small-Angle X-ray Study

We report on the earliest stages of the formation of complexes of calcium phosphate in the presence of the serum protein alpha(2)-HS glycoprotein/fetuin-A termed calciprotein particles (CPPs). Time-resolved small-angle X-ray scattering (TR-SAXS) and stopped-flow analysis were used to monitor the growth of protein mineral particles nucleating from supersaturated salt solutions. It was found that fetuin-A did not influence the formation of mineral nuclei. However, fetuin-A did prevent the aggregation of nuclei and thus mineral precipitation. Hence, fetuin-A shielded spontaneously formed mineral nuclei, leading to stable calciprotein particles in the first stage of mineralization. Fetuin-A is therefore critically required during the earliest stages of the formation of protein-mineral complexes in order to prevent uncontrolled mineralization.