Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts.
Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts.
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DOI：
10.3390/biom11010112
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发表时间：
2021-01-15
期刊：
影响因子：
5.5
通讯作者：
Abu Kwaik Y
中科院分区：
文献类型：
--
作者：
Price CTD;Abu Kwaik Y
泛素途径在生命的真核域中高度保守，在众多的细胞过程中起着至关重要的作用。不足为奇的是，许多细胞内的细菌病原体经常以基本的宿主泛素途径为靶标。嗜肺军团菌胞内细菌向宿主细胞胞浆中注入多种经典的和新型的泛素修饰酶，调节宿主细胞中与泛素相关的各种过程。大多数这些病原体注射的蛋白被指定为效应器，通过含有F-box或U-box结构域来模拟已知的E3-泛素连接酶。作为经典的F-box效应器，AnkB针对宿主蛋白进行K48连锁的多泛素化，这导致蛋白酶体过度降解，这是产生足够的氨基酸供应病原体新陈代谢所必需的。相反，SIDC和SDCA效应子尽管具有E3-泛素连接酶活性，但与已知的真核连接酶没有结构上的相似性，这表明真核生物中E3-连接酶的数量没有得到充分的表达。嗜肺乳杆菌还向宿主体内注入许多新的泛素修饰酶，这些酶是催化靶蛋白丝氨酸残基的磷酸核糖泛素化的辅助效应家族，不依赖于典型的E1-2-3酶系。有趣的是，环境细菌嗜肺乳杆菌已经在作为自然宿主的各种阿米巴物种中进化，而通过受污染的气雾剂意外传播可能会导致人类肺炎。因此，嗜肺乳杆菌新的泛素修饰酶很可能是通过跨界基因转移从不同的自然阿米巴宿主获得的。此外，真核生物中泛素途径的保守使这些新的泛素修饰酶在哺乳动物细胞中具有类似的功能。对这些效应器的生物学功能的研究可能会揭示更新的泛素生物学，并进一步阐明泛素的进化。
The ubiquitin pathway is highly conserved across the eukaryotic domain of life and plays an essential role in a plethora of cellular processes. It is not surprising that many intracellular bacterial pathogens often target the essential host ubiquitin pathway. The intracellular bacterial pathogen Legionella pneumophila injects into the host cell cytosol multiple classes of classical and novel ubiquitin-modifying enzymes that modulate diverse ubiquitin-related processes in the host cell. Most of these pathogen-injected proteins, designated as effectors, mimic known E3-ubiquitin ligases through harboring F-box or U-box domains. The classical F-box effector, AnkB targets host proteins for K48-linked polyubiquitination, which leads to excessive proteasomal degradation that is required to generate adequate supplies of amino acids for metabolism of the pathogen. In contrast, the SidC and SdcA effectors share no structural similarity to known eukaryotic ligases despite having E3-ubiquitin ligase activity, suggesting that the number of E3-ligases in eukaryotes is under-represented. L. pneumophila also injects into the host many novel ubiquitin-modifying enzymes, which are the SidE family of effectors that catalyze phosphoribosyl-ubiquitination of serine residue of target proteins, independently of the canonical E1-2-3 enzymatic cascade. Interestingly, the environmental bacterium, L. pneumophila, has evolved within a diverse range of amoebal species, which serve as the natural hosts, while accidental transmission through contaminated aerosols can cause pneumonia in humans. Therefore, it is likely that the novel ubiquitin-modifying enzymes of L. pneumophila were acquired by the pathogen through interkingdom gene transfer from the diverse natural amoebal hosts. Furthermore, conservation of the ubiquitin pathway across eukaryotes has enabled these novel ubiquitin-modifying enzymes to function similarly in mammalian cells. Studies on the biological functions of these effectors are likely to reveal further novel ubiquitin biology and shed further lights on the evolution of ubiquitin.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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通讯作者：
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