STRUCTURAL STUDIES OF DROSPHILA MIRANDA PROTEIN

细胞不对称分裂是发育中的生物体中实现细胞多样性的一种现象。了解正常情况下细胞不对称分裂的分子机制对于理解肿瘤发生和发育缺陷的起源等异常过程具有重要意义。在果蝇神经母细胞中，这些机制的中心是Miranda，这是一种支架蛋白，负责在有丝分裂过程中不对称地分离细胞命运决定因素。将利用X射线结晶学技术和方法研究米兰达及其与货运蛋白Propero和Staufen的络合物的结构。采用构建筛选策略的合理方法将获得适量的可溶、纯净、稳定、单一的材料。后续的结晶试验将基于稀疏矩阵析因策略。这种“双屏”方法的使用有助于以方便的方式获得衍射质量的晶体，从而可以实现结构确定。

Asymmetric cell division is a phenomenon by which cellular diversity is achieved in the developing organism. Knowledge of the molecular mechanisms by which asymmetric cell division normally occurs is of fundamental importance and relevant to understanding aberrant processes such as tumorigenesis and the origin of developmental defects. Central to these mechanisms in the Drosophila neuroblast is Miranda, a scaffold protein responsible for the asymmetric segregation of cell-fate determinants during mitosis. The structure of Miranda and its complexes with cargo proteins Prospero and Staufen will be investigated utilizing X- ray crystallographic techniques and methodologies. Appropriate quantities of soluble, pure, stable, monodiverse material will be obtained using a rational approach that employs a construct screening strategy. Subsequent crystallization trials will be based on sparse matrix factorial strategies. Use of this "double-screen" approach serves to obtain diffraction quality crystals in an expedient manner so that structure determination may be achieved.