Systems Biology Initiative and School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Australia.
J Proteome Res. 2010 Mar 5;9(3):1218-25. doi: 10.1021/pr900693e.
In proteomics, there is a major challenge in how the functional significance of overexpressed proteins can be interpreted. This is particularly the case when examining proteins in cells or tissues. Here we have analyzed the physicochemical parameters, abundance level, half-life and degree of intrinsic disorder of proteins previously overexpressed in the yeast Saccharomyces cerevisiae. We also examined the interaction domains present and the manner in which overexpressed proteins are, or are not, associated with known complexes. We found a number of protein characteristics were strongly associated with deleterious phenotypes. These included protein abundance (where low-abundance proteins tend to be deleterious on overexpression), intrinsic disorder (where a striking association was seen between percent disorder and degree of deleterious effect), and the number of likely domain-domain interactions. Furthermore, we found a number of domain types, for example, DUF221 and the ubiquitin interaction motif, that were present predominantly in proteins that are deleterious on overexpression. Together, these results provide strong evidence that particular types of proteins are deleterious on overexpression whereas others are not. These factors can be considered in the interpretation of protein expression differences in proteomic experiments.
在蛋白质组学中，如何解释过量表达蛋白质的功能意义是一个主要挑战。当研究细胞或组织中的蛋白质时，尤其如此。在这里，我们分析了先前在酵母酿酒酵母中过量表达的蛋白质的理化参数、丰度水平、半衰期和固有无序度。我们还检查了存在的相互作用结构域，以及过量表达的蛋白质与已知复合物是否相关，以及如何相关。我们发现许多蛋白质特性与有害表型密切相关。这些特性包括蛋白质丰度（低丰度蛋白质在过表达时往往有害）、固有无序（无序百分比与有害效应程度之间存在显著关联）和可能的结构域-结构域相互作用的数量。此外，我们发现了一些结构域类型，例如 DUF221 和泛素相互作用基序，它们主要存在于过表达时有害的蛋白质中。总之，这些结果为特定类型的蛋白质在过表达时是有害的，而其他类型的蛋白质则不是提供了强有力的证据。在蛋白质组学实验中，可以考虑这些因素来解释蛋白质表达差异。
