STRUCTURAL STUDIES OF DROSPHILA MIRANDA PROTEIN

果蝇米兰达蛋白的结构研究

• 批准号: 6385242
• 负责人: JODI M RYTER
• 金额: $ 4.38万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6385242
• 关键词: STRUCTURAL; STUDIES; DROSPHILA; MIRANDA; PROTEIN

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.

不对称细胞分裂是在发育中的生物体中实现细胞多样性的一种现象。了解不对称细胞分裂正常发生的分子机制对理解异常过程（如肿瘤发生和发育缺陷的起源）至关重要。在果蝇神经母细胞中，Miranda是这些机制的核心，它是一种支架蛋白，负责有丝分裂过程中细胞命运决定因素的不对称分离。Miranda及其与货物蛋白Prospero和Staufen的复合物的结构将利用X射线晶体学技术和方法进行研究。适当数量的可溶性，纯的，稳定的，单一的材料将使用合理的方法，采用结构筛选策略获得。后续的结晶试验将基于稀疏矩阵析因策略。使用这种“双筛”方法可以以一种方便的方式获得衍射质量晶体，从而可以实现结构测定。