Protein lysine de-2-hydroxyisobutyrylation by CobB in prokaryotes

Dong, Hanyang; Zhai, Guijin; Chen, Cong; Bai, Xue; Tian, Shanshan; Hu, Deqing; Fan, Enguo; Zhang, Kai

doi:10.1126/sciadv.aaw6703

Cited by 57 publications

(80 citation statements)

References 41 publications

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“…Some writers and erasers in bacteria are versatile in modifications of proteins with various acylations. For examples, CobB has been shown as a de-acetylase in E. coli and as a dehydroxybutyrylase in Proteus mirabilis 50 . Acetylation and succinylation are two representative PTMs in bacteria.…”

Section: Resultsmentioning

confidence: 99%

Crotonylation of key metabolic enzymes regulates carbon catabolite repression in Streptomyces roseosporus

Sun

Zhao

et al. 2020

Commun Biol

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Due to the plethora natural products made by Streptomyces, the regulation of its metabolism are of great interest, whereas there is a lack of detailed understanding of the role of posttranslational modifications (PTM) beyond traditional transcriptional regulation. Herein with Streptomyces roseosporus as a model, we showed that crotonylation is widespread on key enzymes for various metabolic pathways, and sufficient crotonylation in primary metabolism and timely elimination in secondary metabolism are required for proper Streptomyces metabolism. Particularly, the glucose kinase Glk, a keyplayer of carbon catabolite repression (CCR) regulating bacterial metabolism, is identified reversibly crotonylated by the decrotonylase CobB and the crotonyl-transferase Kct1 to negatively control its activity. Furthermore, crotonylation positively regulates CCR for Streptomyces metabolism through modulation of the ratio of glucose uptake/Glk activity and utilization of carbon sources. Thus, our results revealed a regulatory mechanism that crotonylation globally regulates Streptomyces metabolism at least through positive modulation of CCR.

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Section: Resultsmentioning

confidence: 99%

Crotonylation of key metabolic enzymes regulates carbon catabolite repression in Streptomyces roseosporus

Sun

Zhao

et al. 2020

Commun Biol

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“…In this study, 36 we used western blot to demonstrate that Khib is an evolutionarily-conserved PTM in 37 wheat and its donators, with the highest Khib abundance occurring in hexaploidy wheat. 38 Additionally, global profiling using affinity purification and mass spectroscopy of 2-39 hydroxyisobutyrylome revealed that there were 3348 lysine modification sites from 40 1074 proteins in common wheat (Triticum aestivum L.). Moreover, bioinformatic data 41 indicated that Khib proteins participate in a wide variety of biological and metabolic 42 pathways.…”

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confidence: 99%

Global Profiling of 2-hydroxyisobutyrylome in Common Wheat

Zhang

et al. 2020

Preprint

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33As a novel post-translational modification (PTM), lysine 2-hydroxyisobutyrylation 34 (Khib) has been found to play a role in active gene transcription in mammalian cells 35 and yeast, but the function of Khib proteins in plants remains unknown. In this study, 36 we used western blot to demonstrate that Khib is an evolutionarily-conserved PTM in 37 wheat and its donators, with the highest Khib abundance occurring in hexaploidy wheat. 38 Additionally, global profiling using affinity purification and mass spectroscopy of 2-39 hydroxyisobutyrylome revealed that there were 3348 lysine modification sites from 40 1074 proteins in common wheat (Triticum aestivum L.). Moreover, bioinformatic data 41 indicated that Khib proteins participate in a wide variety of biological and metabolic 42 pathways. Immunoprecipitation and western blot confirmed that Khib proteins had an 43 in vivo origin. A comparison of Khib and other major PTMs revealed that Khib proteins 44 were simultaneously modified by multiple PTMs. Using mutagenesis experiments and 45Co-IP, we demonstrated that Khib on K206 is a key regulatory modification of 46 phosphoglycerate kinase enzymatic activity and found that de-Khib on K206 affects 47 protein interactions. Furthermore, Khib production of low-molecular-weight proteins 48 was a response to the deacetylase inhibitors nicotinamide and trichostatin A. This study 49 provides evidence that enhances our current understanding of Khib in wheat plants, 50 including the cooperation between this PTM and metabolic regulation. 51 Introduction 54 Protein post-translational modification (PTM) can change the charge, conformation, 55 and molecular weight of proteins by adding chemical groups to the amino acid residues 56 of a protein that can also expand the biological functions of the protein [1]. PTMs have 57 been found to play a vital role in diverse biological processes by regulating protein 58 function [2]. Lysine acetylation (Kac) is an important PTM that neutralizes positively-59 charged lysine residues; previous studies of Kac have mainly focused on nuclear 60 proteins [3, 4]. Using mass spectrometry, a high abundance of non-histone proteins has 61 been extensively characterized recently [5−9]. Kac is currently known to regulate 62 diverse protein properties, including subcellular localization, DNA-protein interactions, 63 protein stability, protein-protein interactions, and enzymatic activity [7, 8, 10, 11]. With 64 the help of high sensitivity mass spectrometry, there are currently 9 novel lysine PTMs 65 reported, including formylation (Kfor), crotonylation (Kcr), butyrylation (Kbu), 66 succinylation (Ksu), malonylation (Kma), propionylation (Kpr), glutarylation (Kglu), 67 β-hydroxybutyrylation (Kbhb), and 2-hydroxyisobutyrylation (Khib), and the catalog 68 is still growing [12−18]. These novel PTMs have been mainly found in mammalian and 69 yeast cells, and also in plants, such as Arabidopsis thaliana [19], rice [20−23], and 70 tobacco [19, 24]. Increasing evidence suggests that these new types of PTMs are 71 ...

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“…Proteasomes of prokaryotes have been found only in Actinomycetes [ 95 ], where M. tuberculosis is one of the few bacteria known to have proteasomes on which relatively detailed research about mechanism and function has been performed. Its target proteins are involved in multiple aspects, such as substance metabolism in carbon metabolism and fatty acid metabolism, signaling pathways, toxic and antitoxic factors and cell wall and cell membrane components, and are related to the pathogenicity of Mtb [ 27 ]. Therefore, its proteasome is considered a new drug target for Mtb treatment.…”

Section: Pupylationmentioning

confidence: 99%

“…Mtb mainly inhabits host macrophages after infection. Studies have shown that pupylation and the proteasome are key elements that prevent the removal from host macrophages [ 27 , 98 ]. Furthermore, in the Mtb proteasome pathway, Pup serves as a protein modifier and provides an important means for identifying and characterizing Mtb substrates targeted to the proteasome.…”

Section: Pupylationmentioning

confidence: 99%

Regulation of Protein Post-Translational Modifications on Metabolism of Actinomycetes

Sun

Mao

2020

Biomolecules

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Protein post-translational modification (PTM) is a reversible process, which can dynamically regulate the metabolic state of cells through regulation of protein structure, activity, localization or protein–protein interactions. Actinomycetes are present in the soil, air and water, and their life cycle is strongly determined by environmental conditions. The complexity of variable environments urges Actinomycetes to respond quickly to external stimuli. In recent years, advances in identification and quantification of PTMs have led researchers to deepen their understanding of the functions of PTMs in physiology and metabolism, including vegetative growth, sporulation, metabolite synthesis and infectivity. On the other hand, most donor groups for PTMs come from various metabolites, suggesting a complex association network between metabolic states, PTMs and signaling pathways. Here, we review the mechanisms and functions of PTMs identified in Actinomycetes, focusing on phosphorylation, acylation and protein degradation in an attempt to summarize the recent progress of research on PTMs and their important role in bacterial cellular processes.

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Protein lysine de-2-hydroxyisobutyrylation by CobB in prokaryotes

Cited by 57 publications

References 41 publications

Crotonylation of key metabolic enzymes regulates carbon catabolite repression in Streptomyces roseosporus

Crotonylation of key metabolic enzymes regulates carbon catabolite repression in Streptomyces roseosporus

Global Profiling of 2-hydroxyisobutyrylome in Common Wheat

Regulation of Protein Post-Translational Modifications on Metabolism of Actinomycetes

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