Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites

Zhang, Naiwen; Jiang, Ning; Zhang, Kai; Zheng, Lili; Zhang, Di; Sang, Xiaoyu; Feng, Ying; Chen, Ran; Yang, Na; Wang, Xinyi; Cheng, Zhongyi; Suo, Xun; Lun, Zhao‐Rong; Chen, Qijun

doi:10.1016/j.isci.2020.101074

Cited by 36 publications

(56 citation statements)

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“…Investigation of the orthologous proteins in various organisms may elucidate the evolutionary conservation of succinylation. To figure out more features of succinylated events, we performed a comparison of succinylprotein homologs against 8 species with identified succinylomes: V. parahaemolyticus , E. coli , Trypanosoma brucei , S. cerevisiae , Magnaporthe oryzae , M. musculus , H. sapiens , and Oryza sativa ( Weinert et al, 2013 ; Pan et al, 2015 ; Zhen et al, 2016 ; Wang et al, 2019 ; Zhang et al, 2020 ). A total of 297 succinylated proteins in S. epidermidis were found orthologs in these 8 species.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, we compared the 13 identified motifs in S. epidermidis with previously reported succinylomes in E. coli , V. parahaemolyticus , T. brucei , S. cerevisiae , M. oryzae , M. musculus , H. sapiens , and O. sativa (see Figure 7 and Supplementary Table 9 ; Weinert et al, 2013 ; Pan et al, 2015 ; Zhen et al, 2016 ; Wang et al, 2019 ; Zhang et al, 2020 ). The pattern of K at the + 1 site around succinyllysine was identified in E. coli , Hela cells, and yeast.…”

Section: Resultsmentioning

confidence: 99%

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Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis

et al. 2021

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BackgroundLysine succinylation is a newly identified posttranslational modification (PTM), which exists widely from prokaryotes to eukaryotes and participates in various cellular processes, especially in the metabolic processes. Staphylococcus epidermidis is a commensal bacterium in the skin, which attracts more attention as a pathogen, especially in immunocompromised patients and neonates by attaching to medical devices and forming biofilms. However, the significance of lysine succinylation in S. epidermidis proteins has not been investigated.ObjectivesThe purpose of this study was to investigate the physiological and pathological processes of S. epidermidis at the level of PTM. Moreover, by analyzing previous succinylome datasets in various organisms, we tried to provide an in-depth understanding of lysine succinylation.MethodsUsing antibody affinity enrichment followed by LC-MS/MS analysis, we examined the succinylome of S. epidermidis (ATCC 12228). Then, bioinformatics analysis was performed, including Gene Ontology (GO), KEGG enrichment, motif characterization, secondary structure, protein–protein interaction, and BLAST analysis.ResultsA total of 1557 succinylated lysine sites in 649 proteins were identified in S. epidermidis (ATCC 12228). Among these succinylation proteins, GO annotation showed that proteins related to metabolic processes accounted for the most. KEGG pathway characterization indicated that proteins associated with the glycolysis/gluconeogenesis and citrate cycle (TCA cycle) pathway were more likely to be succinylated. Moreover, 13 conserved motifs were identified. The specific motif KsuD was conserved in model prokaryotes and eukaryotes. Succinylated proteins with this motif were highly enriched in the glycolysis/gluconeogenesis pathway. One succinylation site (K144) was identified in S-ribosylhomocysteine lyase, a key enzyme in the quorum sensing system, indicating the regulatory role succinylation may play in bacterial processes. Furthermore, 15 succinyltransferases and 18 desuccinylases (erasers) were predicted in S. epidermidis by BLAST analysis.ConclusionWe performed the first comprehensive profile of succinylation in S. epidermidis and illustrated the significant role succinylation may play in energy metabolism, QS system, and other bacterial behaviors. This study may be a fundamental basis to investigate the underlying mechanisms of colonization, virulence, and infection of S. epidermidis, as well as provide a new insight into regulatory effects succinylation may lay on metabolic processes (Data are available via ProteomeXchange with identifier PXD022866).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis

et al. 2021

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“…A recent study (published while this article was under review) has identified the histone PTMs associated with the distinctive T. cruzi parasite life forms, with over 60 PTM fluctuations during the life cycle ( 17 ). Two independent studies (one of which was published while this article was under review) have recently unearthed more than 150 PTMs on T. brucei histones also ( 18 , 19 ). Strikingly, virtually no acetylation marks were detectable in H3.V and H4.V.…”

Section: Landscape Of Histone Modifications In Trypanosomatidsmentioning

confidence: 99%

Histone Modifications and Other Facets of Epigenetic Regulation in Trypanosomatids: Leaving Their Mark

Saha

2020

mBio

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Histone posttranslational modifications (PTMs) modulate several eukaryotic cellular processes, including transcription, replication, and repair. Vast arrays of modifications have been identified in conventional eukaryotes over the last 20 to 25 years. While initial studies uncovered these primarily on histone tails, multiple modifications were subsequently found on the central globular domains as well. Histones are evolutionarily conserved across eukaryotes, and a large number of their PTMs and the functional relevance of these PTMs are largely conserved. Trypanosomatids, however, are early diverging eukaryotes. Although possessing all four canonical histones as well as several variants, their sequences diverge from those of other eukaryotes, particularly in the tails. Consequently, the modifications they carry also vary. Initial analyses almost 15 years ago suggested that trypanosomatids possessed a smaller collection of histone modifications. However, exhaustive high resolution mass spectrometry analyses in the last few years have overturned this belief, and it is now evident that the “histone code” proposed by Allis and coworkers in the early years of this century is as complex in these organisms as in other eukaryotes. Trypanosomatids cause several diseases, and the members of this group of organisms have varied lifestyles, evolving diverse mechanisms to evade the host immune system, some of which have been found to be principally controlled by epigenetic mechanisms. This minireview aims to acquaint the reader with the impact of histone PTMs on trypanosomatid cellular processes, as well as other facets of trypanosomatid epigenetic regulation, including the influence of three-dimensional (3D) genome architecture, and discusses avenues for future investigations.

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“…Post-translational modification (PTM) mapping information was obtained from available online datasets: phosphorylation during the T. brucei (procyclic form) cell cycle 14 , post-translational modification of T. brucei and T. b. evansi bloodstream forms 15 , differential phosphorylation analysis between bloodstream and procyclic stage of T. brucei 16 , phosphorylation in the TbDYRK knock-out strain of T. brucei 17 , phosphorylation events during heat shock 18 , comparative analysis of lysine acetylation in trypanosomes 19 , arginine methylation in slender forms of T. brucei 20 , arginine methylation in mitochondria of T. brucei 21 .…”

Section: Methodsmentioning

confidence: 99%

A global analysis of low-complexity regions in the Trypanosoma brucei proteome reveals enrichment in the C-terminus of nucleic acid binding proteins providing potential targets of phosphorylation

Cayla¹,

Matthews²,

Ivens³

2020

Wellcome Open Res

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Background: Low-complexity regions (LCRs) on proteins have attracted increasing attention recently due to their role in the assembly of membraneless organelles or granules by liquid-liquid phase separation. Several examples of such granules have been shown to sequester RNA and proteins in an inactive state, providing an important mechanism for dynamic post-transcriptional gene regulation. In trypanosome parasites, post-transcriptional control overwhelmingly dominates gene regulation due to the organisation of their genome into polycistronic transcription units. The purpose of the current study was to generate a substantially more comprehensive genome-wide survey of LCRs on trypanosome proteins than currently available . Methods: Using the Shannon’s entropy method, provided in the R package ‘entropy’, we identified LCRs in the proteome of Trypanosoma brucei. Our analysis predicts LCRs and their positional enrichment in distinct protein cohorts and superimposes on this a range of post-translational modifications derived from available experimental datasets. Results: We have identified 8162 LCRs present on 4914 proteins, representing 42% of the proteome, placing Trypanosoma brucei among the eukaryotes with the highest percentage of LCRs. Our results highlight the enrichment of LCRs in the C-terminal region of predicted nucleic acid binding proteins, these acting as favoured sites for potential phosphorylation. Phosphorylation represents 51% of the post-translational modifications present on LCRs compared to 16% on the rest of the proteome. Conclusions: The post-translational modifications of LCRs, and in particular phosphorylation events, could contribute to post-transcriptional gene expression control and the dynamics of protein targeting to membraneless organelles in kinetoplastid parasites.

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Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites

Cited by 36 publications

References 53 publications

Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis

Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis

Histone Modifications and Other Facets of Epigenetic Regulation in Trypanosomatids: Leaving Their Mark

A global analysis of low-complexity regions in the Trypanosoma brucei proteome reveals enrichment in the C-terminus of nucleic acid binding proteins providing potential targets of phosphorylation

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