Decoding of genome function and evolution based on the 3D structures of proteins

基于蛋白质 3D 结构解码基因组功能和进化

• 批准号: 12208006
• 负责人: GO Mitiko
• 金额: $ 72.19万
• 依托单位: Nagahama Institute of Bio-Science and Technology (2003-2004)Nagoya University (2000-2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12208006/
• 关键词: Prediction of genome function; Module; 3D-keynote; Cyanobacterium genome; Human genome annotation; Sugar-protein interaction; Hydrophobic cluster; Alternative splicing; タンパク質間ネットワーク; HetPDB-Navi; RNA・タンパク質相互作用; FAMSBASE; タンパク質-RNA相互作用; 水和; タ

As a functional prediction method for ORFs inferred in genome sequences, we developed a method to convert structural and functional properties of protein modules into amino acid sequence patterns, called "3D-keynote". Using the method, we inferred a function of ORF, slr0197 from a cyanobacterium genome, which was subsequently verified by collaborative experiments. Furthermore, we made an automatic system to generate 3D-keynotes for each kind of functions and accomplished generations of 196 kinds of 3D-keynotes, whose prediction accuracies were evaluated to be about 85% on an average. Applying these to a cyanobacterium genome, we obtained clues for inferring the functions for about 12% of function-unknown ORFs. The 3D-keynotes were also used for human genome annotation in H-invitational (Yura ＆ Go).A sugar-protein interaction prediction system was developed. Strict and loose evaluations of the prediction accuracy resulted in 25 and 66%, respectively, which were better than other existin … More g methods. To experimentally verify the prediction system, crystal structure analyses of sugar-binding proteins such as lectin, were done. We determined structures of six novel complex forms of congerin and obtained evidences supporting the existence of sugar-binding sites predicted by the prediction system (Shirai).A chain topology of hydrophobic cluster residues was found to be a reduced representation of a whole chain of the protein molecule. From molecular dynamics simulations of a pseudo-peptide chain composed of hydrophobic cluster residues and cluster analyses of the generated structures, we defined roles of hydrophobic cluster residues as their non-specific hydrophobic aggregation forces made the protein chain compact to decrease the search space for conformations and accelerate the folding process (Soda).Exhaustively analyzing human full-length cDNA data by the method we developed to identify alternative splicing (AS) regions, we found that most regions altered by AS were shorter than common sizes of protein domains, and indicated possibilities that AS of transcripts may lead to structural destabilization of and/or loss of interaction sites on their protein products and result in changing pathways of the protein network involved (Go ＆ Takahashi). Less

作为在基因组序列中推断ORF的功能预测方法，我们开发了一种将蛋白质模块的结构和功能特性转换为氨基酸序列模式的方法，称为“3D-keynote”。利用该方法，我们从蓝藻基因组中推断出 ORF slr0197 的功能，并随后通过合作实验进行了验证。此外，我们还制作了针对每种功能的3D主题自动生成系统，并完成了196种3D主题的生成，其预测准确率平均在85%左右。将这些应用于蓝藻基因组，我们获得了推断约 12% 功能未知 ORF 功能的线索。 3D主题演讲还用于H邀请赛（Yura＆Go）中的人类基因组注释。开发了糖-蛋白质相互作用预测系统。严格和宽松的预测精度评估结果分别为 25% 和 66%，优于其他现有方法。为了通过实验验证预测系统，对糖结合蛋白（例如凝集素）进行了晶体结构分析。我们确定了六种新的康姜素复合形式的结构，并获得了支持预测系统（Shirai）预测的糖结合位点存在的证据。发现疏水性簇残基的链拓扑是蛋白质分子全链的简化表示。通过对由疏水簇残基组成的伪肽链的分子动力学模拟和对生成结构的簇分析，我们定义了疏水簇残基的作用，因为它们的非特异性疏水聚集力使蛋白质链紧凑，减少构象搜索空间并加速折叠过程（Soda）。通过我们的方法彻底分析人类全长 cDNA 数据。 开发用于识别选择性剪接（AS）区域，我们发现大多数被AS改变的区域比蛋白质结构域的常见大小短，并且表明转录物的AS可能导致其蛋白质产物上的相互作用位点的结构不稳定和/或丢失，并导致所涉及的蛋白质网络的途径发生变化（Go＆Takahashi）。较少的

项目成果

An empirical approach for detecting nucleotide-binding sites on proteins

• DOI: 10.1093/protein/gzj002
• 发表时间: 2006-02-01
• 期刊: PROTEIN ENGINEERING DESIGN & SELECTION
• 影响因子: 2.4
• 作者: Saito, M;Go, M;Shirai, T
• 通讯作者: Shirai, T

モジュールに基づく機能予測-3Dキーノート

基于模块的特征预测 - 3D 主题演讲

• 发表时间: 2002
• 期刊: 蛋白質核酸酵素 47(8)
• 作者: 由良 敬;郷 通子
• 通讯作者: 郷 通子

由良 敬, 郷 通子: "ジンクフィンガードメイン"生体の科学 モチーフ・ドメインリスト. 52・5. 394-395 (2001)

Takashi Yura，Michiko Go：“锌指结构域”生物科学主题/结构域列表 52・5（2001）。

The use of ACORN in solving a 39.5 kDa macromolecule with 1.9 A resolution laboratory source data.

使用 ACORN 以 1.9 A 分辨率实验室源数据解析 39.5 kDa 大分子。

• 发表时间: 2004
• 期刊: Journal of Synchrotoron Radiation 11
• 作者: V.Rajakannan;S.Selvanayagam;T.Yamane;T.Shirai;T.Kobayashi;S.Ito;D.Velmurugan
• 通讯作者: D.Velmurugan

Enlarged FAMSBASE : protein 3D structure models of genome sequences for 41 species

扩大的 FAMSBASE：41 个物种基因组序列的蛋白质 3D 结构模型

• 发表时间: 2003
• 期刊: Nucleic Acids Research 31
• 作者: Yamaguchi;A.;Iwadate;M.;Suzuki;E.;Yura;K.;Kawakita;S.;Umeyama;H.;Go;M.
• 通讯作者: M.