Amelogenesis Imperfecta Is Related to Decreased Amelogenin-MMP20 Interactions

Amelogenin with a proline 41 to threonine mutation (P41T) is hydrolyzed at a lower rate by matrix metalloproteinase 20 (MMP20), resulting in amelogenesis imperfecta (AI).  Objective: The aim of this study was to elucidate the effect of P41T on the interactions between amelogenin and MMP20, which may contribute to the formation of this type of AI.  Methods: The interactions of a recombinant wild-type human amelogenin and its P41T mutant with recombinant human MMP20s were compared by substrate competition assay, pull-down assay, isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) analyses. Results: The results showed that binding of the P41T mutant amelogenin to MMP20 was significantly lower than that of wild-type amelogenin. Conclusion: Our study supports a model in which the P41T mutation reduces the interactions between amelogenin and MMP20, leading to decreased degradation of amelogenin by MMP20 and resulting in AI.  Support: Supported by grant R01DE015821, R01DE017529 and R01DE13508 from NIDCR.