A N ‐terminus domain determines amelogenin’s stability to guide the development of mouse enamel matrix

AbstractAmelogenins, the principal proteins in the developing enamel microenvironment, self ‐assemble into supramolecular structures to govern the remodeling of a proteinaceous organic matrix into longitudinally ordered hydroxyapatite nanocrystal arrays. Extensivein vitro studies using purified native or recombinant proteins have revealed the potential of N ‐terminal amelogenin on protein self‐assembly and its ability to guide the mineral deposition. We have previously identified a 14‐aa domain (P2) of N‐terminal amelogenin that can self‐assemble into amyloid‐like fibrilsin vitro. Here we investigated how this domain affects the ability of amelogenin self ‐assembling and stability of enamel matrix protein scaffolding in anin vivo animal model. Mice harboring mutant amelogenin lacking P2 domain had a hypoplastic, hypomineralized and aprismatic enamel.In vitro, the mutant recombinant amelogenin without P2 had a reduced tendency to self ‐assemble and was prone to accelerated hydrolysis by MMP20, the prevailing metalloproteinase in early developing enamel matrix. A reduced amount of amelogenins and a lack of elongated fibrous assemblies in the development enamel matrix of mutant mice were evident as compared to that in the wild ty pe mouse enamel matrix. Our study is the first to demonstrate that a subdomain (P2) at the N‐terminus of amelogenin controls amelogenin’s assembly into a transient protein scaffold that resists rapid proteolysis during enamel devel...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research