Bioinformatics linkage of protein disorder and function

蛋白质紊乱与功能的生物信息学联系

基本信息

批准号：
7123059
负责人：
ALAN KEITH DUNKER
金额：
$ 32.62万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7123059
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

项目摘要

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）：总体目标是了解内在障碍和蛋白质功能之间的关系。缺乏数据和缺乏注释已经限制了我们以前的研究，因此第一个目标是扩大和详尽注释我们的有序和无序的蛋白质数据库。使用带注释的数据，我们提议将不同的生物信息学和数据策略进行比较，以找到秩序/障碍问题的最佳方法。即使目前的数据不完整和注释，我们也能够发现100多个无序蛋白质区域至少执行28个不同的功能，分为四个广泛类别：分子识别，蛋白质修饰，熵链和分子组装 /拆卸。本文提出了几项实验，以进一步了解这些类别的前三个类别的疾病/功能关系：1。分子识别：要检验的假设是，参与信号转导和CELT调节的蛋白质通常使用内在疾病来识别其结合靶标的； 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); 3。熵链::要测试的假设是mRNA中的替代剪接主要发生在编码无序蛋白的区域，因为该位置避免了与不同长度的成功折叠相关的困难，但相同的蛋白质相同。拟议的研究对人类疾病，尤其是各种癌症具有重要意义，因为正如我们最近所表明的那样，许多甚至大多数与癌症相关的蛋白质具有重要的内在疾病区域。

项目成果

期刊论文数量（84）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of intrinsically disordered proteins with electrospray ionization mass spectrometry: conformational heterogeneity of alpha-synuclein.

DOI：
10.1002/prot.22604
发表时间：
2010-02-15
期刊：
Proteins
影响因子：
2.9
作者：
Frimpong AK;Abzalimov RR;Uversky VN;Kaltashov IA
通讯作者：
Kaltashov IA

High-throughput characterization of intrinsic disorder in proteins from the Protein Structure Initiative.

DOI：
10.1016/j.jsb.2012.05.013
发表时间：
2012-10
期刊：
JOURNAL OF STRUCTURAL BIOLOGY
影响因子：
3
作者：
Johnson, Derrick E.;Xue, Bin;Sickmeier, Megan D.;Meng, Jingwei;Cortese, Marc S.;Oldfield, Christopher J.;Le Gall, Tanguy;Dunker, A. Keith;Uversky, Vladimir N.
通讯作者：
Uversky, Vladimir N.

Understanding protein non-folding.