Amelogenins, the major
protein component of the mineralizing enamel extracellular matrix, are critical for normal enamel formation as documented in the linkage studies of a group of inherited disorders, with defective enamel formation, called
Amelogenesis imperfecta. Recent cases of
Amelogenesis imperfecta include mutations that resulted in truncated
amelogenin protein lacking the hydrophilic C-terminal
amino acids. Current advances in knowledge on
amelogenin structure,
nanospheres assembly and their effects on crystal growth have supported the hypothesis that
amelogenin nanospheres provide the organized microstructure for the initiation and modulated growth of enamel
apatite crystals. In order to evaluate the function of the conserved hydrophilic C-terminal telopeptide during enamel biomineralization, the present study was designed to analyze the self-assembly and
apatite binding behavior of
amelogenin proteins and their
isoforms lacking the hydrophilic C-terminal. We applied dynamic light scattering to investigate the size distribution of
amelogenin nanospheres formed by a series of native and
recombinant proteins. In addition, the
apatite binding properties of these
amelogenins were examined using commercially available
hydroxyapatite crystals.
Amelogenins lacking the carboxy-terminal (native P161 and recombinant rM166) formed larger
nanospheres than those formed by their full-length precursors: native P173 and recombinant rM179. These data suggest that after removal of the hydrophilic carboxy-terminal segment further association of the
nanospheres takes place through hydrophobic interactions. The affinity of
amelogenins lacking the carboxy-terminal regions to
apatite crystals was significantly lower than their parent
amelogenins. These structure-functional analyses suggest that the hydrophilic carboxy-terminal plays critical functional roles in mineralization of enamel and that the lack of this segment causes abnormal mineralization.