Disordered Conformation with Low Pii Helix in Phosphoproteins Orchestrates Biomimetic Apatite Formation

The interplay between noncollagenous proteins and biomineralization is widely accepted, yet the contribution of their secondary structure in mineral formation remains to be clarified. This study demonstrates a role for phosvitin, an intrinsically disordered phosphoprotein, in chick embryo skeletal development, and using circular dichroism and matrix least-squares Henderson–Hasselbalch global fitting, unravels three distinct pH-dependent secondary structures in phosvitin. By sequestering phosvitin on a biomimetic 3D insoluble cationic framework at defined pHs, access is gained to phosvitin in various conformational states. Induction of biomimetic mineralization at near physiological conditions reveals that a disordered secondary structure with a low content of P_II helix is remarkably efficient at promoting calcium adsorption, and results in the formation of biomimetic hydroxyapatite through an amorphous calcium phosphate precursor. By extending this finding to phosphorylated full-length human recombinant dentin matrix protein-1 (17-513 AA), this bioinspired approach provides compelling evidence for the role of a disordered secondary structure in phosphoproteins in bone-like apatite formation.

Biomineralization is the process by which mineral phase is deposited in living systems in the presence of protein mediators. Avian and mammalian phosphoproteins with a low-P_II-helix-containing disordered secondary structure are more efficient at binding calcium complexes and mediating formation of bone-like hydroxyapatite (HAp) in comparison to a β-sheet-dominated secondary structure. The formation of this biomimetic HAp occurs via amorphous nanosphere precursors.

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