Lysine methylation shields an intracellular pathogen from ubiquitylation and autophagy.
Lysine methylation shields an intracellular pathogen from ubiquitylation and autophagy.
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赖氨酸甲基化保护细胞内病原体免受泛素化和自噬的影响。
DOI：
10.1126/sciadv.abg2517
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发表时间：
2021-06
期刊：
影响因子：
13.6
通讯作者：
Welch MD
中科院分区：
文献类型：
--
作者：
Engström P;Burke TP;Tran CJ;Iavarone AT;Welch MD
赖氨酸甲基化使细菌病原体免受宿主泛素攻击。许多细胞内病原体避免被它们的宿主细胞检测到。然而，它们如何避免被泛素标记仍然是未知的，这是导致抗菌自噬的初始步骤。在这里，我们表明，细胞内的细菌病原体巴氏立克次体使用两个蛋白质赖氨酸甲基转移酶（PKMT）修改外膜蛋白（OMP），并防止其泛素化。缺乏PKMT的突变体在小鼠中是无毒的，并且由于泛素化和自噬靶向而不能在巨噬细胞中生长。赖氨酸甲基化保护丰富的表面蛋白OmpB从细菌表面的泛素依赖性耗尽。赖氨酸甲基化组的分析表明，PKMT通过在被宿主泛素修饰的相同位点处的甲基化来修饰OMP的子集，包括OmpB。这些发现表明，赖氨酸甲基化是立克次体发病机制的一个重要决定因素，它可以保护细菌蛋白免于泛素化以逃避自噬靶向。
Lysine methylation camouflages a bacterial pathogen from the host ubiquitin attack. Many intracellular pathogens avoid detection by their host cells. However, it remains unknown how they avoid being tagged by ubiquitin, an initial step leading to antimicrobial autophagy. Here, we show that the intracellular bacterial pathogen Rickettsia parkeri uses two protein-lysine methyltransferases (PKMTs) to modify outer membrane proteins (OMPs) and prevent their ubiquitylation. Mutants deficient in the PKMTs were avirulent in mice and failed to grow in macrophages because of ubiquitylation and autophagic targeting. Lysine methylation protected the abundant surface protein OmpB from ubiquitin-dependent depletion from the bacterial surface. Analysis of the lysine-methylome revealed that PKMTs modify a subset of OMPs, including OmpB, by methylation at the same sites that are modified by host ubiquitin. These findings show that lysine methylation is an essential determinant of rickettsial pathogenesis that shields bacterial proteins from ubiquitylation to evade autophagic targeting.
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影响因子：
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