2024年8月16日，Nature Communications期刊在线发表了题为“A protein O-GlcNAc glycosyltransferase regulates the antioxidative response in Yersinia pestis”的研究论文。作者发现：HmwC在鼠疫杆菌中充当O-GlcNAc转移酶（OGT），负责多种蛋白质的O-GlcNAc糖基化修饰。这篇文章提供了关于鼠疫杆菌中O-GlcNAc糖基化修饰系统的新见解，并为理解细菌如何通过蛋白质糖基化来适应不同的环境压力提供了重要的分子基础。

    中文摘要： 蛋白质上的O-连接的N-乙酰葡萄糖胺修饰（O-GlcNAc糖基化）在真核生物中通常与各种应激反应和细胞过程相关，但其在细菌中的潜在作用尚不清楚。这项研究中，作者展示了蛋白质HmwC作为O-GlcNAc转移酶（OGT）的作用，负责鼠疫杆菌（Yersinia pestis）中多种蛋白质的O-GlcNAc糖基化修饰。鼠疫杆菌是一种通过跳蚤传播的病原体，是导致瘟疫的致病菌。作者在模拟哺乳动物宿主（Mh）和跳蚤媒介（Fv）环境的条件下，鉴定了64个O-GlcNAc修饰的蛋白质（包括65个糖基化位点），它们在丰度上存在差异。hmwC编码假定的 OGT，在结构上与 GT41 家族的任何现有成员不同，其缺失会导致O-GlcNAc修饰减少、生长减缓以及在压力下毒力特性和生存能力发生改变。纯化的HmwC可以使用UDP-GlcNAc作为糖基化供体在体外修饰靶蛋白。其中一个靶蛋白OsdY的糖基化，促进了鼠疫杆菌在氧化应激条件下的存活。因此，以上研究结果支持：O-GlcNAc糖基化修饰调节抗氧化反应可能是原核生物和真核生物共有的保守过程。

  英文摘要：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.

DOI：https://doi.org/10.1038/s41467-024-50959-w 

原文链接：https://www.nature.com/articles/s41467-024-50959-w 

参考文献：Cao, S., Wang, T., Ren, Y. et al. A protein O-GlcNAc glycosyltransferase regulates the antioxidative response in Yersinia pestis. Nat Commun 15, 7062 (2024).