Global Lysine Crotonylation and 2-Hydroxyisobutyrylation in Phenotypically Different Toxoplasma gondii Parasites

Yin, David; Jiang, Ning; Zhang, Yue; Wang, Dawei; Sang, Xiaoyu; Feng, Ying; Chen, Rang; Wang, Xinyi; Yang, Na; Chen, Qijun

doi:10.1074/mcp.ra119.001611

Cited by 37 publications

(57 citation statements)

References 71 publications

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“…Lysine crotonylation and 2hydroxyisobutyrylation occurred on proteins mainly located in the cytosol of both parasites and RBCs, mediating diverse metabolic pathways (Fig. S3A and B), similar to our previous findings in Toxoplasma gondii(23). For the RBC proteins, acylation including acetylation, crotonylation, and 2-hydroxyisobutyrylation mainly occurred in proteins associated with sugar metabolism, such as in glycolysis/gluconeogenesis and pentose phosphate pathways, and oxidative stress, proteasome, de novo protein folding, hypoxia-inducible factor (HIF)-1 signaling pathway, and cadherin binding.…”

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confidence: 90%

“…were predominant in the early stages (Supplemental Data S12, and to be further analyzed in a later section). This indicated that in the early stage of P. falciparum development, not only phosphorylation and acetylation (28) but also 2hydroxyisobutyrylation may exert similar functions in gene activation, as was also observed in a recent study of T. gondii (23). In addition, the heat shock protein 70 (HSP70) family members were mainly modified by 2-hydroxyisobutyrylation apart from phosphorylation and crotonylation in Cluster 1 (Supplemental Data S12); they are known to be important in protein homoeostasis and protein trafficking across the PV as chaperones and immunogens (29,30).…”

Section: The Overall Ptmomics Of P Falciparum and Infected Erythrocytessupporting

confidence: 76%

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Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes

Wang

Jiang

Sang

et al. 2021

Molecular & Cellular Proteomics

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Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo a myriad number of posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective de-modification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.

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confidence: 90%

Section: The Overall Ptmomics Of P Falciparum and Infected Erythrocytessupporting

confidence: 76%

Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes

Wang

Jiang

Sang

et al. 2021

Molecular & Cellular Proteomics

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“…The yeast histone acetyltransferase complex NuA4 and human acetyltransferase Tip60 have been shown to function as enzymes to catalyze K hib , while histone deacetylase 2 (HDAC2) and histone deacetylase 3 (HDAC3) function as the major enzymes to remove 2hydroxyisobutyryl from K hib in mammalian cells (Huang et al, 2018), suggesting that there may be an internal relation between K ac and K hib . In recent years, K hib has been detected and characterized in both histone and non-histone proteins in several species using newly developed modern techniques in molecular biology and mass spectrometry (Huang et al, 2017;Meng et al, 2017;Yu et al, 2017;Dong et al, 2018;Yin et al, 2019). For example, a total of 6,548 unique K hib sites on 1,725 proteins were identified in human cells (Huang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in the Phytopathogenic Fungus Botrytis cinerea

Liang

et al. 2020

Front. Microbiol.

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Posttranslational modifications (PTMs) of the whole proteome have become a hot topic in the research field of epigenetics, and an increasing number of PTM types have been identified and shown to play significant roles in different cellular processes. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly detected PTM, and the 2-hydroxyisobutyrylome has been identified in several species. Botrytis cinerea is recognized as one of the most destructive pathogens due to its broad host distribution and very large economic losses; thus the many aspects of its pathogenesis have been continuously studied. However, distribution and function of Khib in this phytopathogenic fungus are not clear. In this study, a proteome-wide analysis of Khib in B. cinerea was performed, and 5,398 Khib sites on 1,181 proteins were identified. Bioinformatics analysis showed that the 2-hydroxyisobutyrylome in B. cinerea contains both conserved proteins and novel proteins when compared with Khib proteins in other species. Functional classification, functional enrichment and protein interaction network analyses showed that Khib proteins are widely distributed in cellular compartments and involved in diverse cellular processes. Significantly, 37 proteins involved in different aspects of regulating the pathogenicity of B. cinerea were detected as Khib proteins. Our results provide a comprehensive view of the 2-hydroxyisobutyrylome and lay a foundation for further studying the regulatory mechanism of Khib in both B. cinerea and other plant pathogens.

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“…Recently, an evolutionarily conserved short-chain lysine acylation modification dubbed lysine 2-hydroxyisobutylation (K hib ) has been reported, which introduces a steric bulk with a mass shift of +86.03 Da ( Supplementary Figure 1A ) and neutralize the positive charge of lysine ( Dai et al, 2014 ; Xiao et al, 2015 ). It involves various biological functions including biosynthesis of amino acids, starch biosynthesis, carbon metabolism, glycolysis / gluconeogenesis and transcription ( Dai et al, 2014 ; Huang et al, 2017 , 2018a ; Li et al, 2017 ; Meng et al, 2017 ; Yu et al, 2017 ; Wu et al, 2018 ; Yin et al, 2019 ). For instance, the decrease of this modification on K281 of glycolytic enzyme ENO1 reduces its catalytic activity ( Huang et al, 2018b ).…”

Section: Introductionmentioning

confidence: 99%

DeepKhib: A Deep-Learning Framework for Lysine 2-Hydroxyisobutyrylation Sites Prediction

Zhang

Zou

et al. 2020

Front. Cell Dev. Biol.

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As a novel type of post-translational modification, lysine 2-Hydroxyisobutyrylation (K hib) plays an important role in gene transcription and signal transduction. In order to understand its regulatory mechanism, the essential step is the recognition of K hib sites. Thousands of K hib sites have been experimentally verified across five different species. However, there are only a couple traditional machine-learning algorithms developed to predict K hib sites for limited species, lacking a general prediction algorithm. We constructed a deep-learning algorithm based on convolutional neural network with the one-hot encoding approach, dubbed CNN OH. It performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the ROC curve (AUC) values for CNN OH ranged from 0.82 to 0.87 for different organisms, which is superior to the currently available K hib predictors. Moreover, we developed the general model based on the integrated data from multiple species and it showed great universality and effectiveness with the AUC values in the range of 0.79-0.87. Accordingly, we constructed the on-line prediction tool dubbed DeepKhib for easily identifying K hib sites, which includes both species-specific and general models. DeepKhib is available at http://www.bioinfogo.org/DeepKhib.

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Global Lysine Crotonylation and 2-Hydroxyisobutyrylation in Phenotypically Different Toxoplasma gondii Parasites

Cited by 37 publications

References 71 publications

Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes

Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes

Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in the Phytopathogenic Fungus Botrytis cinerea

DeepKhib: A Deep-Learning Framework for Lysine 2-Hydroxyisobutyrylation Sites Prediction

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