4.7 Article

Global Insights Into Lysine Acylomes Reveal Crosstalk Between Lysine Acetylation and Succinylation in Streptomyces coelicolor Metabolic Pathways

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MOLECULAR & CELLULAR PROTEOMICS
卷 20, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.mcpro.2021.100148

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资金

  1. National Key R&D Program of China [2019YFA0904003]
  2. Strategic Priority Research Program of the Chinese Academy of Sciences, China [XDB38020300]
  3. National Natural Science Foundation of China [31921006, 82000273]
  4. Guangdong Basic and Applied Basic Research Foundation [2021A1515012511]
  5. China Postdoctoral Science Foundation [BX20200092]

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The study identified abundant and dynamic acetylation in Streptomyces coelicolor, suggesting a possible competitive relationship with succinylation in regulating cell physiology. Knockout experiments and in vitro assays confirmed the regulatory crosstalk between the two sirtuins, laying a foundation for further characterization of lysine acetylation and succinylation interactions.
Lysine acylations are reversible and ubiquitous post-translational modifications that play critical roles in regulating multiple cellular processes. In the current study, highly abundant and dynamic acetylation, besides succinylation, was uncovered in a soil bacterium, Streptomyces coelicolor. By affinity enrichment using anti-acetyl-lysine antibody and the following LC-MS/MS analysis, a total of 1298 acetylation sites among 601 proteins were identified. Bioinformatics analyses suggested that these acetylated proteins have diverse subcellular localization and were enriched in a wide range of biological functions. Specifically, a majority of the acetylated proteins were also succinylated in the tricarboxylic acid cycle and protein translation pathways, and the bimodification occurred at the same sites in some proteins. The acetylation and succinylation sites were quantified by knocking out either the deacetylase ScCobB1 or the desuccinylase ScCobB2, demonstrating a possible competitive relationship between the two acylations. Moreover, in vitro experiments using synthetically modified peptides confirmed the regulatory crosstalk between the two sirtuins, which may be involved in the collaborative regulation of cell physiology. Collectively, these results provided global insights into the S. coelicolor acylomes and laid a foundation for characterizing the regulatory roles of the crosstalk between lysine acetylation and succinylation in the future.

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