Structural Studies of MCM Complex

MCM复合体的结构研究

基本信息

批准号：
8204543
负责人：
XIAOJIANG S CHEN
金额：
$ 32.55万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2013-11-30
项目状态：
已结题

项目摘要

Project Summary: Structural studies of MCM complex Minichromosome maintenance protein (MCM) complex functions as a helicase that unwinds DNA to provide template for DNA replication and plays a critical role in regulating cell growth. MCM helicases are considered to be a licensing factor for cellular DNA replication. MCM proteins from eukaryotes and archaea form hexamers ring complex, with MWt approximating 0.5-1.0 Mega Dolton. Despite extensive efforts, gap of knowledge exists in our understanding of how MCM unwinds DNA, how MCM interacts with DNA during unwinding, and how ATP is utilized to drive the conformational changes of MCM needed for unwinding. MCM are conserved in archaea and eukaryotes. Eukaryotic MCM contains six homologs that form hetero-hexamer and possibly higher order complexes. However, the MCM complex in some archaea contains only one MCM protein that can assemble into homo-hexamers or dodecamers. Thus, archaeal MCM homo-oligomers provide a simpler system for understanding the structure/function of MCM complex. The goal of this proposal is to use archaeal MCM complexes as a model system to understand the structure/functions of MCM complex, with particular emphasis on the mechanisms regarding oligomerization, ATP-triggered conformational changes, and DNA binding and remodeling functions of MCM proteins. A combination of structural biology, biophysics, and functional biochemistry will be employed for the study. The resulting data will provide valuable information for understanding the DNA unwinding mechanism at the replication fork. It will also provide structural/functional insights for the homologous eukaryotic MCM complex, which bears high relevance to cell growth regulation and cancer biology.

项目摘要：MCM复合物的结构研究微小浓度维持蛋白（MCM）复合物充当放松DNA的解旋酶为DNA复制提供模板，并在调节细胞生长中起关键作用。 MCM 解旋酶被认为是细胞DNA复制的许可因素。 MCM蛋白来自真核生物和古细菌形式六聚体环复合物，MWT近似于0.5-1.0兆多尔顿。尽管做出了广泛的努力，但知识差距仍然存在于我们对MCM的理解中放开DNA，在放松过程中如何与DNA相互作用，以及如何利用ATP驱动放松所需的MCM的构象变化。 MCM在古细菌和真核生物。真核MCM包含六种形成异己的同源物，甚至可能更高订购复合物。但是，某些古细菌中的MCM复合物仅包含一个MCM蛋白可以组装成同伴有的杂物或十足。因此，古细菌MCM Homo-Oligomers 提供一个更简单的系统来了解MCM复合物的结构/功能。目标该建议是使用古细菌MCM复合物作为模型系统来了解 MCM复合物的结构/功能，特别强调有关的机制寡聚，ATP触发的构象变化以及DNA结合和重塑 MCM蛋白的功能。结构生物学，生物物理学和功能性的结合这项研究将采用生物化学。结果数据将为了解复制叉处的DNA解开机制。它也将提供同源真核MCM复合物的结构/功能见解，该复合物具有很高与细胞生长调节和癌症生物学相关。