Amelogenin protein exhibits a modular design: Implications for form and function
Amelogenin protein exhibits a modular design: Implications for form and function
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DOI：
10.1080/03008200390152089
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Snead, ML
中科院分区：
文献类型：
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作者：
Snead, ML
形成釉质的最丰富的蛋白质是釉原蛋白，一种能够自组装形成纳米球的蛋白质。人类釉原蛋白基因中自然发生的突变是导致至少一些统称为成釉不全（AI）的疾病实体的原因，尽管很明显AI表型可能是由负责釉细胞外基质生物发生的其他基因的改变引起的。在釉原蛋白的功能结构域中产生变化的突变确实对釉质生物矿化产生不利影响。表型模仿几种已知AI突变的釉原蛋白的蛋白质工程表现出自组装缺陷。发生在釉原蛋白结构域中的氨基酸改变似乎会导致“矿物质缺陷”，也就是说釉质的钙化不足，而发生在釉原蛋白分子另一个结构域中的突变会导致“发育不良缺陷”，即釉质厚度的减少。然而，并不是所有具有AI表型的患者都精确地分离到这些任意指定[1，2]。尽管如此，将含有特定突变的釉原蛋白的结构域与釉质结构改变的类型相关联表明了釉原蛋白的模块化设计，这通过使用重组DNA技术的蛋白质工程和转基因动物研究得到了证实[3]。
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].