Journal Article

Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif

Osickova, Adriana, Sebo, Peter, Spoutil, Frantisek, Sedlacek, Radislav, Prochazkova, Michaela, Benada, Oldrich, Bumba, Ladislav, Klein, Ophir D., Kasparek, Petr, Osicka, Radim, Wald, Tomas, Prochazka, Jan

2017

Overview

The formation of mineralized tissues is governed by extracellular matrix proteins that assemble into a 3D organic matrix directing the deposition of hydroxyapatite. Although the formation of bones and dentin depends on the self-assembly of type I collagen via the Gly-X-Y motif, the molecular mechanism by which enamel matrix proteins (EMPs) assemble into the organic matrix remains poorly understood. Here we identified a Y/F-x-x-Y/L/F-x-Y/F motif, evolutionarily conserved from the first tetrapods to man, that is crucial for higher order structure self-assembly of the key intrinsically disordered EMPs, ameloblastin and amelogenin. Using targeted mutations in mice and high-resolution imaging, we show that impairment of ameloblastin self-assembly causes disorganization of the enamel organic matrix and yields enamel with disordered hydroxyapatite crystallites. These findings define a paradigm for the molecular mechanism by which the EMPs self-assemble into supra-molecular structures and demonstrate that this process is crucial for organization of the organic matrix and formation of properly structured enamel.

• Publisher: National Academy of Sciences
• Subject: Amelogenin - metabolism / Amino Acid Motifs - physiology / Amino Acid Sequence / Animals / Biological Evolution / Biological Sciences / Collagen / Dental Enamel - metabolism / Dental Enamel Proteins - metabolism / Durapatite - metabolism / Enamel / Evolution / Extracellular Matrix Proteins - metabolism / Intrinsically Disordered Proteins - metabolism / Male / Mice / Molecular structure / Mutation / PNAS Plus / Protein Binding - physiology / Proteins / Tissues