BIOLOGY AND BIOMETRICS OF ENAMEL CRYSTAL GROWTH

描述(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含量最丰富的蛋白质。先前 我们已经证明了釉原蛋白形成了三维的复合体 超结构与釉质晶体的形成密切相关(Diekwich等人)。 1993年、1995年、1998年的迪克维希)。完整的釉原蛋白结构的关键作用 对健康牙釉质的作用在最近的遗传学研究中得到了强调 证明釉原蛋白单点突变会导致牙釉质缺陷 受影响的个人(Collier等人1997年)。为了获得理解 釉原蛋白分子的特定结构域如何影响釉原蛋白 在牙釉质生物矿化过程中的作用我们设计了一项研究计划 检测和模拟釉原蛋白在何处、何时以及如何形成具有重要功能 元结构，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 通过特定的基序和结构域直接决定釉质的形成 釉原蛋白超分子组织。具体目标：1.界定 釉原蛋白和釉质蛋白酶在发育过程中的时空框架 釉质基质。2.测定釉原蛋白和釉质蛋白酶的功能 器官培养中牙釉质的生物矿化。3.确定主题和地点 在细胞培养中支配釉原蛋白超分子组织的。4.至 用X射线测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理解 釉原蛋白在釉质生物矿化过程中的作用 有助于加深对釉质形成的临床症状的理解 以及在开发重要的临床辅助设备方面 牙釉质修复牙釉质丢失或患病的修复和再生

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.