Bioinformatics linkage of protein disorder and function

蛋白质紊乱与功能的生物信息学联系

• 批准号: 6950310
• 负责人: ALAN KEITH DUNKER
• 金额: $ 32.44万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950310
• 关键词: RNA splicing; biological signal transduction; data collection methodology /evaluation; genome; intermolecular interaction; mathematics; messenger RNA; molecular biology information system; molecular shape; nuclear magnetic resonance spectroscopy; phosphorylation; protein binding; protein protein interaction; protein sequence; protein structure function; thermodynamics

DESCRIPTION (provided by applicant): The overall goal is to understand the relationships between intrinsic disorder and protein function. Lack of data and lack of annotation have limited our previous research, so the first aims will be to enlarge and exhaustively annotate our ordered and disordered protein databases. Using the annotated data, we propose next to compare different bioinformatics and datamining strategies to find the optimal approach for the order/disorder problem. Even with the current incomplete data and annotation, we were able to discover that more than 100 disordered protein regions carry out at least 28 distinct functions that fall into four broad categories: molecular recognition, protein modification, entropic chains, and molecular assembly /disassembly. Several experiments are proposed herein to further understanding of disorder/function relationships for the first three of these categories: 1. Molecular recognition: the hypothesis to be tested is that proteins involved in signal transduction and celt regulation commonly use intrinsic disorder for recognizing their binding targets; 2. Protein modification: the hypothesis to be tested is that chemical modification primarily involves residues that are located within intrinsically disordered regions possibly due to the requirement for disorder-to-order transitions as the targets fold onto to their modifying enzymes (special emphasis will be placed on phosphorylation, but g!ycosylation, acetylation, ubiquitination, and other modifications, will be considered as time permits); and 3. Entropic chains:: the hypothesis to be tested is that alternative splicing in mRNAs occurs mostly in regions that code for disordered protein because this location circumvents difficulties associated with the successful folding of different length, but otherwise identical proteins. The proposed research has important implications for human disease, especially various cancers, for as we have recently shown, many and probably the large majority of cancer-associated proteins have significant regions of intrinsic disorder.

描述（由申请人提供）：