Development of a method to predict protein function based on module classification

开发基于模块分类的蛋白质功能预测方法

基本信息

批准号：
11480189
负责人：
GO Mitiko
金额：
$ 9.28万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

项目摘要

The aim of this study is (1) to clarify that key components of protein functions are localized to compact short segments, modules, and (2) to elucidate principle of protein design using modules as building blocks. In consequence, we found various kinds of protein functions were assigned to modules. For example, (1) the functional sites of the catalytic domain of family 10 xylanase are localized to some of the modules; (2) in many case, ligands for certain metal ions exist within one or two modules. Furthermore, modules with similar structure and function are frequently observed in various proteins, which indicates the possibility that the modules were shuffled. In addition, (3) common modules are found to be used for protein-protein interaction; (4) only two modules are used in subunit interaction of hemoglobin, which could explain why subunit interactions of hemoglobin are diversified in various lineage. We also showed that modules can be deleted or shuffled by experiments. For example, (1) module M2 in barnase was deleted without loss of the stable three-dimensional structure similar to the native structure and the cooperative folding behavior. (2) a chimera xylanase, which was made by exchange of module M10 between two kinds of xylanases in family 10, maintained the structure and function, though the enzyme activity decrease by a tenth. This study has clarified a basic principle for module-based protein design from both views of computer science and experimental science.

这项研究的目的是（1）阐明蛋白质功能的关键组成部分被本地化为紧凑的短段，模块和（2），以使用模块作为构建块来阐明蛋白质设计的原理。因此，我们发现将各种蛋白质功能分配给模块。例如，（1）家族10木聚糖酶的催化结构域的功能部位定位于某些模块；（2）在许多情况下，某些金属离子的配体在一个或两个模块中存在。此外，在各种蛋白质中经常观察到具有相似结构和功能的模块，这表明模块被洗牌的可能性。此外，（3）发现常见模块用于蛋白质 - 蛋白质相互作用；（4）在血红蛋白的亚基相互作用中仅使用了两个模块，这可以解释为什么血红蛋白的亚基相互作用在各种谱系中多样化。我们还表明，可以通过实验删除或洗牌模块。例如，（1）巴尔纳斯中的模块M2被删除，而不会损失与天然结构和合作折叠行为相似的稳定的三维结构。（2）一种嵌合二甲烷酶是通过在家族10中两种木聚糖酶之间交换模块M10来维持的结构和功能，尽管酶活性降低了十分之一。这项研究阐明了从计算机科学和实验科学的观点中阐明了基于模块的蛋白质设计的基本原理。