| First Author | Wald T | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 9 | Pages | E1641-E1650 |
| PubMed ID | 28196895 | Mgi Jnum | J:241593 |
| Mgi Id | MGI:5903162 | Doi | 10.1073/pnas.1615334114 |
| Citation | Wald T, et al. (2017) Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif. Proc Natl Acad Sci U S A 114(9):E1641-E1650 |
| abstractText | 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 supramolecular structures and demonstrate that this process is crucial for organization of the organic matrix and formation of properly structured enamel. |
