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小鼠肝脏赖氨酸丁烯酰化的全局分析

Global Lysine Crotonylation Profiling of Mouse Liver.

机构信息

State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Research Unit of Proteomics and Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing, 102206, China.

出版信息

Proteomics. 2020 Oct;20(19-20):e2000049. doi: 10.1002/pmic.202000049. Epub 2020 Sep 24.

DOI:10.1002/pmic.202000049
PMID:32864800
Abstract

Lysine crotonylation (Kcr) is a recently discovered post-translational modification that potentially regulates multiple biological processes. With an objective to expand the available crotonylation datasets, LC-MS/MS is performed using mouse liver samples under normal physiological conditions to obtain in vivo crotonylome. A label-free strategy is used and 10 034 Class I (localization probabilities > 0.75) crotonylated sites are identified in 2245 proteins. The KcrE, KcrD, and EKcr motifs are significantly enriched in the crotonylated peptides. The identified crotonylated proteins are mostly enzymes and primarily located in the cytoplasm and nucleus. Functional enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes shows that the crotonylated proteins are closely related to the purine-containing compound metabolic process, ribose phosphate metabolic process, carbon metabolism pathway, ribosome pathway, and a series of metabolism-associated biological processes. To the best of the authors' knowledge, this research provides the first report on the mouse liver crotonylome. Furthermore, it offers additional evidence that crotonylation exists in non-histone proteins, and is likely involved in various biological processes. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium with the dataset identifiers PXD019145.

摘要

赖氨酸丁酰化(Kcr)是一种新发现的翻译后修饰,可能调节多种生物学过程。本研究旨在扩展现有的丁酰化数据集,在正常生理条件下使用小鼠肝组织样本进行 LC-MS/MS 实验,以获得体内丁酰化组。本研究采用无标记策略,在 2245 种蛋白质中鉴定到 10034 个 Class I(定位概率>0.75)丁酰化位点。丁酰化肽中富含 KcrE、KcrD 和 EKcr 基序。鉴定到的丁酰化蛋白主要是酶,主要位于细胞质和细胞核中。基于基因本体论和京都基因与基因组百科全书的功能富集分析表明,丁酰化蛋白与含嘌呤的化合物代谢过程、核糖磷酸代谢过程、碳代谢途径、核糖体途径以及一系列与代谢相关的生物学过程密切相关。据作者所知,本研究首次报道了小鼠肝丁酰化组。此外,本研究进一步证实了丁酰化存在于非组蛋白中,并可能参与多种生物学过程。该研究的质谱蛋白质组学数据已在 ProteomeXchange 联盟的数据集标识符 PXD019145 中进行了存储。

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