An Evolutionarily Conserved Subdomain in Amelotin Promotes Amorphous Calcium Phosphate-to-Hydroxyapatite Phase Transition

Amelotin (AMTN) has been shown to promote hydroxyapatite (HAP) formation in the late stages of tooth enamel biomineralization, but the molecular mechanisms that control this process are poorly understood. Here, by the use of high-resolution Raman spectroscopy and atomic force microscopy to directly observe time-resolved in situ crystallization, we show that AMTN facilitates the in vitro formation of HAP crystals by promoting phase transformation from amorphous calcium phosphate (ACP) as a naturally occurring HAP precursor in enamel. In the presence of a near-physiological enamel fluid, mineral conversions of ACP proceed through dissolution and recrystallization at the ACP–fluid interface, where the adsorbed AMTN promotes the ACP dissolution through a strong complexation of the AMTN protein with calcium ions, occurring even in supersaturated solutions. Single-molecule measurements of equilibrium rupture force and the binding free-energy of AMTN adsorbed to four calcium phosphate phases identify a highly co...