Threonine phosphorylation fine-tunes the regulatory activity of histone-like nucleoid structuring protein in Salmonella transcription

Lizhi Hu, Wei Kong, Dezhi Yang, Qiangqiang Han, Lin Guo, Yixin Shi

Research output: Contribution to journalArticle

Abstract

Histone-like nucleoid structuring protein (H-NS) in enterobacteria plays an important role in facilitating chromosome organization and functions as a crucial transcriptional regulator for global gene regulation. Here, we presented an observation that H-NS of Salmonella enterica serovar Typhimurium could undergo protein phosphorylation at threonine 13 residue (T13). Analysis of the H-NS wild-type protein and its T13E phosphomimetic substitute suggested that T13 phosphorylation lead to alterations of H-NS structure, thus reducing its dimerization to weaken its DNA binding affinity. Proteomic analysis revealed that H-NS phosphorylation exerts regulatory effects on a wide range of genetic loci including the PhoP/PhoQ-regulated genes. In this study, we investigated an effect of T13 phosphorylation of H-NS that rendered transcription upregulation of the PhoP/PhoQ-activated genes. A lower promoter binding of the T13 phosphorylated H-NS protein was correlated with a stronger interaction of the PhoP protein, i.e., a transcription activator and also a competitor of H-NS, to the PhoP/PhoQ-dependent promoters. Unlike depletion of H-NS which dramatically activated the PhoP/PhoQ-dependent transcription even in a PhoP/PhoQ-repressing condition, mimicking of H-NS phosphorylation caused a moderate upregulation. Wild-type H-NS protein produced heterogeneously could rescue the phenotype of T13E mutant and fully restored the PhoP/PhoQ-dependent transcription enhanced by T13 phosphorylation of H-NS to wild-type levels. Therefore, our findings uncover a strategy in S. typhimurium to fine-tune the regulatory activity of H-NS through specific protein phosphorylation and highlight a regulatory mechanism for the PhoP/PhoQ-dependent transcription via this post-translational modification.

Original languageEnglish (US)
Article number1515
JournalFrontiers in Microbiology
Volume10
Issue numberJUL
DOIs
StatePublished - Jan 1 2019

Fingerprint

Threonine
Salmonella
Histones
Phosphorylation
Proteins
Up-Regulation
Genetic Loci
Salmonella enterica
Dimerization
Enterobacteriaceae
Post Translational Protein Processing
Regulator Genes

Keywords

  • Bacterial signal transduction
  • Histone-like nucleoid structuring protein (H-NS)
  • Post-translational modification
  • Protein threonine phosphorylation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Threonine phosphorylation fine-tunes the regulatory activity of histone-like nucleoid structuring protein in Salmonella transcription. / Hu, Lizhi; Kong, Wei; Yang, Dezhi; Han, Qiangqiang; Guo, Lin; Shi, Yixin.

In: Frontiers in Microbiology, Vol. 10, No. JUL, 1515, 01.01.2019.

Research output: Contribution to journalArticle

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