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内在无序功能选集。1. 具有长无序区域的蛋白质的生物学过程和功能。

Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions.

作者信息

Xie Hongbo, Vucetic Slobodan, Iakoucheva Lilia M, Oldfield Christopher J, Dunker A Keith, Uversky Vladimir N, Obradovic Zoran

机构信息

Center for Information Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.

出版信息

J Proteome Res. 2007 May;6(5):1882-98. doi: 10.1021/pr060392u. Epub 2007 Mar 29.

Abstract

Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical approach, outlines the major findings, and provides illustrative examples of biological processes and functions positively and negatively correlated with intrinsic disorder.

摘要

确定功能、氨基酸序列和蛋白质结构之间的关系是一项重大挑战。在本研究中,我们提出了一种生物信息学方法,该方法可在Swiss-Prot数据库中识别与内在无序相关的功能关键词。采用统计评估对这些相关性的显著性进行排名。考虑了蛋白质序列数据冗余以及蛋白质长度与蛋白质结构之间的关系,以确保统计推断的质量。使用此方法分析了Swiss-Prot数据库中的20多万种蛋白质。使用长无序区域的PONDR VL3E预测器进行内在无序预测,其准确率超过86%。总体而言,在至少与20种蛋白质相关的710个Swiss-Prot功能关键词中,发现238个与预测的长内在无序区域呈强正相关,而302个与这些区域呈强负相关。其余170个关键词不明确,与无序预测没有强正相关或负相关。这些功能涵盖了各种各样的生物活性,这意味着无序区域具有广泛的功能谱。我们的结果与文献研究结果非常吻合,因为我们能够为绝大多数与内在无序呈最强正相关或负相关的关键词找到至少一个实验显示的功能无序或有序的说明性例子。这项工作开启了三篇系列论文,丰富了当前对蛋白质结构-功能关系的认识,特别是关于内在无序蛋白质的功能,并为研究人员提供了一种新工具,可用于增进对蛋白质结构与功能之间关系的理解。该系列的第一篇论文描述了我们的统计方法,概述了主要发现,并提供了与内在无序呈正相关和负相关的生物过程和功能的说明性例子。

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