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A protein O-GlcNAc glycosyltransferase regulates the antioxidative response in Yersinia pestis

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  • Shiyang Cao

    (Academy of Military Medical Sciences)

  • Tong Wang

    (Academy of Military Medical Sciences)

  • Yifan Ren

    (Academy of Military Medical Sciences)

  • Gengshan Wu

    (Academy of Military Medical Sciences)

  • Yuan Zhang

    (Academy of Military Medical Sciences)

  • Yafang Tan

    (Academy of Military Medical Sciences)

  • Yazhou Zhou

    (Academy of Military Medical Sciences)

  • Hongyan Chen

    (Academy of Military Medical Sciences)

  • Yu Zhang

    (Academy of Military Medical Sciences)

  • Yajun Song

    (Academy of Military Medical Sciences)

  • Ruifu Yang

    (Academy of Military Medical Sciences)

  • Zongmin Du

    (Academy of Military Medical Sciences)

Abstract

Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC, encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes.

Suggested Citation

  • Shiyang Cao & Tong Wang & Yifan Ren & Gengshan Wu & Yuan Zhang & Yafang Tan & Yazhou Zhou & Hongyan Chen & Yu Zhang & Yajun Song & Ruifu Yang & Zongmin Du, 2024. "A protein O-GlcNAc glycosyltransferase regulates the antioxidative response in Yersinia pestis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50959-w
    DOI: 10.1038/s41467-024-50959-w
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    References listed on IDEAS

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    1. Michael B. Lazarus & Yunsun Nam & Jiaoyang Jiang & Piotr Sliz & Suzanne Walker, 2011. "Structure of human O-GlcNAc transferase and its complex with a peptide substrate," Nature, Nature, vol. 469(7331), pages 564-567, January.
    2. Jorge E. Galán & Hans Wolf-Watz, 2006. "Protein delivery into eukaryotic cells by type III secretion machines," Nature, Nature, vol. 444(7119), pages 567-573, November.
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