BIOLOGY AND BIOMETRICS OF ENAMEL CRYSTAL GROWTH

说明（申请人提供）：本申请的目的是 深入了解结构与功能的关系， 釉原蛋白是牙釉质发育过程中最丰富的蛋白质。先前 我们已经证明釉原蛋白形成复杂的三维结构， 与釉质晶体形成密切相关的超结构（Diekwisch et al. 1993，1995，Diekwisch 1998）。完整的釉原蛋白结构的关键作用 在最近的遗传学研究中， 这表明釉原蛋白单点突变导致牙釉质缺损， 受影响的个体（Collier et al. 1997）。为了得到理解 釉原蛋白分子的特定结构域如何影响釉原蛋白 在釉质生物矿化过程中的作用，我们设计了一个研究计划， 检测和建模釉原蛋白在何处、何时以及如何形成功能重要 亚结构以及它们如何在 蛋白水解酶、糖基化底物和生长的影响 羟基磷灰石晶体。假设：AMEL基因发挥其功能相关 通过特定的图案和结构域直接决定釉质的形成 釉原蛋白超分子结构。具体目标：1。来定义 釉原蛋白和釉蛋白酶在发育中的时空框架 釉质基质2.测定釉原蛋白和釉质蛋白酶在牙釉质发育过程中的功能， 器官培养中的釉质生物矿化。3.为了确定主题和地点 控制细胞培养中釉原蛋白超分子组织。4.到 用X射线确定釉原蛋白的三维结构 结晶学这些实验将提供实验数据来了解 釉原蛋白在釉质生物矿化过程中的作用， 转化为对釉质发生的临床症状的增强理解 以及在发展重要的临床艾滋病， 修复和再生丢失或患病的牙釉质。

DESCRIPTION (provided by applicant): The purpose of the present application is to gain an in-depth understanding of the structure-function relationships of amelogenin, the most abundant protein in developing dental enamel. Previously we have demonstrated that amelogenin forms complex 3-dimensional suprastructures intimately linked to enamel crystal formation (Diekwisch et al. 1993, 1995, Diekwisch 1998). The crucial role of an intact amelogenin structure for healthy tooth enamel has been highlighted in recent genetic studies demonstrating that amelogenin single-point mutations cause enamel defects in affected individuals (Collier et al. 1997). In order to gain an understanding of how specific structural domains of the amelogenin molecule affect amelogenin function during enamel biomineralization we have designed a research plan to detect and model where, when, and how amelogenins form functionally important metastructures and how they substantially change their configuration under the influence of proteolytic enzymes, glycosylated substrates, and growing hydroxyapatite crystals. Hypothesis: The AMEL gene exerts its function related to enamel formation through specific motifs and domains that directly determine amelogenin supramolecular organization. Specific Aims: 1. To define the temporospatial framework of amelogenins and enamel proteases in the developing enamel matrix. 2. To determine amelogenin and enamel protease function during enamel biomineralization in organ culture. 3. To determine the motifs and sites that govern amelogenin supramolecular organization in cell culture. 4. To determine the 3-dimensional structure of amelogenin using X-ray crystallography. These experiments will provide experimental data to understand the role of amelogenin proteins during enamel biomineralization, which will translate in an enhanced understanding of the clinical symptoms of Amelogenesis imperfecta as well as in the development of important clinical aids in the repair and regeneration of lost or diseased enamel.