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剖析念珠菌的发病机制:热带假丝酵母蛋白质组的翻译后修饰。

Dissecting Candida Pathobiology: Post-Translational Modifications on the Candida tropicalis Proteome.

机构信息

1 Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University) , Mangalore, India .

2 Institute of Bioinformatics , International Technology Park, Bangalore, India .

出版信息

OMICS. 2018 Aug;22(8):544-552. doi: 10.1089/omi.2018.0093.

Abstract

Candida tropicalis belongs to the non-albicans group of Candida, and causes epidermal, mucosal, or systemic candidiasis in immunocompromised individuals. Although the prevalence of candidiasis has increased worldwide and non-albicans Candida (NAC) are becoming more significant, there are very few studies that focus on the NAC biology. Proteins and their post-translational modifications (PTMs) are an integral aspect in the pathobiology of such medically important fungi. Previously, we had reported the largest proteomic catalog of C. tropicalis. Notably, PTMs can be identified from proteomics data without a priori enrichment for a particular PTM, thus allowing broad-scale omics analyses. In this study, we developed the "PTM-Pro," a graphical user interface-based tool for identification and summary of high-confidence PTM sites based on statistical threshold of users' choice. We mined available proteomic data of C. tropicalis, and using PTM-Pro identified nearly 600 high-confidence PTM sites. The PTMs identified include phosphorylation of serine, threonine, and tyrosine; acetylation, crotonylation, methylation, and succinylation of lysine. These PTMs reside on biologically significant molecules, including histones, enzymes, and transcription factors. To our knowledge, this is the first report of PTMs in C. tropicalis and lays a foundation for future investigations of C. tropicalis PTMs. In addition, the PTM-Pro offers a graphical user interface tool for research on PTM sites in the field of proteomics.

摘要

热带假丝酵母属于非白假丝酵母组,会导致免疫功能低下个体的表皮、黏膜或全身念珠菌病。尽管世界各地的念珠菌病患病率都有所增加,非白假丝酵母(NAC)也变得越来越重要,但关注 NAC 生物学的研究却很少。蛋白质及其翻译后修饰(PTM)是这些具有重要医学意义的真菌病理生物学的一个重要方面。此前,我们已经报道了最大的热带假丝酵母蛋白质组目录。值得注意的是,PTM 可以从蛋白质组学数据中鉴定出来,而无需对特定 PTM 进行预先富集,从而可以进行广泛的组学分析。在这项研究中,我们开发了“PTM-Pro”,这是一种基于图形用户界面的工具,用于根据用户选择的统计阈值识别和总结高可信度 PTM 位点。我们挖掘了可用的热带假丝酵母蛋白质组学数据,并使用 PTM-Pro 鉴定了近 600 个高可信度 PTM 位点。鉴定出的 PTM 包括丝氨酸、苏氨酸和酪氨酸的磷酸化;赖氨酸的乙酰化、巴豆酰化、甲基化和琥珀酰化。这些 PTM 存在于具有生物学意义的分子上,包括组蛋白、酶和转录因子。据我们所知,这是首次在热带假丝酵母中报道 PTM,为未来对热带假丝酵母 PTM 的研究奠定了基础。此外,PTM-Pro 为蛋白质组学领域的 PTM 位点研究提供了一种图形用户界面工具。

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