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

Area of Science:

• Biochemistry
• Developmental Biology
• Materials Science

Background:

• Mineralized tissue formation relies on extracellular matrix proteins organizing hydroxyapatite deposition.
• Type I collagen self-assembly via the Gly-X-Y motif governs bone and dentin formation.
• The self-assembly mechanism of enamel matrix proteins (EMPs) is poorly understood.

Purpose of the Study:

• To identify the molecular mechanism governing the self-assembly of enamel matrix proteins (EMPs).
• To investigate the role of a conserved motif in EMP higher-order structure formation.
• To understand the impact of EMP self-assembly defects on enamel organic matrix organization and hydroxyapatite deposition.

Main Methods:

• Identification of a conserved Y/F-x-x-Y/L/F-x-Y/F motif in ameloblastin and amelogenin.
• Targeted mutagenesis studies in mice.
• High-resolution imaging techniques.

Main Results:

• The identified motif is evolutionarily conserved and crucial for the self-assembly of ameloblastin and amelogenin.
• Impaired ameloblastin self-assembly leads to disorganized enamel organic matrix.
• Defects in self-assembly result in enamel with disordered hydroxyapatite crystallites.

Conclusions:

• A paradigm for EMP self-assembly into supramolecular structures has been defined.
• EMP self-assembly is critical for organizing the organic matrix during enamel formation.
• Properly structured enamel formation depends on the precise self-assembly of EMPs.