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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480189/
• 关键词: Module classification; shuffling; Intron; Membrane protein; peroxiclase; Metal ion; Nucleic acid interaction; Function finetuning; ペルオキシダーゼ; モジュール; ゲノム情報; ヘモグロビン; サブユニット接触; タンパク質機能; モジュールシャッフリング; タンパク質相互作用; 金属イオン結合; ミニバルナ-ゼ; フィコシアニン; リン

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.

本研究的目的是（1）阐明蛋白质功能的关键组分定位于紧凑的短片段，模块，和（2）阐明蛋白质设计的原则，使用模块作为构建块。结果发现，各种蛋白质的功能被分配到模块。例如，（1）家族10木聚糖酶的催化结构域的功能位点定位于一些模块;（2）在许多情况下，某些金属离子的配体存在于一个或两个模块内。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，这表明模块被改组的可能性。另外，（3）蛋白质间相互作用的模块有共同的;（4）血红蛋白亚基间相互作用的模块只有两个，这可以解释血红蛋白亚基间相互作用在不同谱系中的多样性。我们还表明，模块可以删除或洗牌的实验。例如，（1）芽孢杆菌RNA酶中的模块M2被删除，而不丧失与天然结构相似的稳定三维结构和协同折叠行为。(2)第10家族的两种木聚糖酶通过交换M10模块而得到的嵌合木聚糖酶，其结构和功能保持不变，但酶活下降了十分之一。本研究从计算机科学和实验科学的角度阐明了基于模块的蛋白质设计的基本原理。

项目成果

Kei Yura et al.: "Putative Mechanism of Natural Transformation as Deduced from Genome Data."DNA Research. 6・2. 75-82 (1999)

Kei Yura 等人：“从基因组数据推论的自然转化的推定机制”。DNA Research 6・2（1999）。

Yamaguchi, A.et al.: "Enlarged FAMSBASE : 3D protein structure models of genome sequences for 41 species."Nucleic Acids Research. 31. 463-468 (2003)

Yamaguchi, A.等人：“放大的 FAMSBASE：41 个物种基因组序列的 3D 蛋白质结构模型。”核酸研究。

Kaneko, S. et al.: "An Investigation of the Nature and Function of Module 10 in a Family F/10 Xylanase FXYN of Streptomyces olivaceoviridjs E-86 by Module Shuffling with the Cex of Cellulomonas fimi and by Site-Directed Mutagenesis."FEBS Letters. 460. 61-

Kaneko, S. 等人：“通过使用纤维单胞菌 Cex 进行模块改组和定点诱变，对链霉菌 F/10 木聚糖酶 FXYN 家族 F/10 中的模块 10 的性质和功能进行研究。”

郷 通子: "遺伝子構造の進化とプロテオーム"学術月報. 55. 1141-1147 (2002)

吴美智子：《基因结构和蛋白质组的进化》学术月报55。1141-1147（2002）。

郷 通子: "遺伝子構造の進化とプロテオーム解析"学術月報. 55・15. 1141-1147 (2002)

吴美智子：“基因结构的进化和蛋白质组分析”学术月报55・1147（2002）。