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

基本信息

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

项目摘要

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的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，称为“ 3D-KYNOTE”。使用该方法，我们从蓝细菌基因组中推断出ORF，SLR0197的函数，随后通过协作实验对此进行了验证。此外，我们制作了一个自动系统，以生成每种功能和196种3D-keynotes的几代人的3D键，评估其预测准确性的平均值约为85％。将这些应用于蓝细菌基因组，我们获得了推断大约12％不知名ORF的功能的线索。 3D键也用于H-vitational（Yura＆Go）中的人类基因组注释。开发了糖蛋白相互作用预测系统。对预测准确性的严格评估分别导致了25％和66％，这比其他现有方法更好。为了实验验证预测系统，完成了糖结合蛋白（例如讲座）的晶体结构分析。我们确定了六种新型复杂形式的结构，并获得了支持预测系统预测的糖结合位点的证据（Shirai）。疏水簇保留的链拓扑被发现是蛋白质分子的整个链的降低的表示。我们从分子动力学模拟中的伪肽链组成，该链链由疏水簇残留物和簇分析所产生的结构的簇分析，我们确定了疏水簇残留物的作用我们开发了为识别替代剪接（AS）区域的开发，我们发现大多数区域都比蛋白质结构域的常见大小变化，并且表明可能导致其蛋白质产品上的结构性不稳定和/或涉及蛋白质网络途径变化的蛋白质途径的结构不稳定和/或导致涉及蛋白质途径的结构稳定（Go＆Takahahashi）。较少的

项目成果

期刊论文数量（206）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of KaiC phosphorylation in the circadian clock system of Synechococcus elongatus PCC 7942

DOI：
10.1073/pnas.0403906101
发表时间：
2004-09-21
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Nishiwaki, T;Satomi, Y;Kondo, T
通讯作者：
Kondo, T

"structure and properties of water ", "models for water molecules", "hydration of biomolecules ", "structural analysis of nonnative status ", "structural fluctuation and experimentally observable quantities"

“水的结构和性质”、“水分子模型”、“生物分子的水合作用”、“非原生状态的结构分析”、“结构涨落和实验可观测量”