Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif.
Proc Natl Acad Sci U S A
; 114(9): E1641-E1650, 2017 02 28.
Article
em En
| MEDLINE
| ID: mdl-28196895
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Motivos de Aminoácidos
/
Esmalte Dentário
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Proteínas Intrinsicamente Desordenadas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
República Tcheca