Amelogenin Protein Exhibits a Modular Design: Implications for Form and Function

Abstract

The most abundant protein of forming enamel is amelogenin, a protein capable of self-assembly to form nanospheres. Naturally occurring mutations in the human amelogenin gene are responsible for at least some of the disease entities known collectively as amelogenesis imperfecta (AI), although it is clear that the AI phenotype may be caused by alteration to other genes responsible for the biogenesis of the enamel extracellular matrix. Mutations that create changes in the functional domains of the amelogenin protein do adversely affect enamel biomineralization. Protein engineering of amelogenin that phenocopies several of the known AI mutations exhibits defects in self-assembly. Amino acid alterations that occur within a domain of amelogenin appear to cause "mineral defects," that is to say hypocalcification of the enamel, whereas mutations that occur elsewhere in another domain of the amelogenin molecule result in "hypoplastic defects," a decrease in thickness of the enamel. However, not all patients with AI phenotypes segregate precisely into these arbitrary designations [1, 2]. Nonetheless, correlating the domain of the amelogenin protein that contains a specific mutation with the type of enamel structural alteration suggests a modular design for amelogenin that is corroborated by protein engineering using recombinant DNA techniques and transgenic animal studies [3].