Photorhabdus antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of 23S ribosomal RNA.

Photorhabdus antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of 23S ribosomal RNA.
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发光杆菌抗菌Rhs多态性毒素通过ADP-核糖基化23 S核糖体RNA抑制翻译。

DOI:
10.1093/nar/gkab608
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发表时间:
2021-08-20
影响因子:
14.9
通讯作者:
Cascales E
Cascales E
中科院分区:
生物学2区
文献类型:
--
作者:
Jurėnas D;Payelleville A;Roghanian M;Turnbull KJ;Givaudan A;Brillard J;Hauryliuk V;Cascales E

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细菌已经发展出了复杂的机制,可以将有效的毒素输送到细菌竞争者或真核细胞中,以破坏竞争对手并获得特定的利基市场或劫持宿主中的必要代谢或信号通路。传递的效应子具有各种活性,例如核酸酶,磷脂酶,肽聚糖水解酶,耗尽NADH或ATP池的酶,损害细胞分裂机械或宿主细胞细胞骨架。在多态性毒素家族中分类的效应子具有模块化结构,其中毒素结构域与其他用作货物的元素融合在一起,以使效应子适应特定的分泌机械。在这里,我们表明,昆虫病原体Photorhabdus laumondii通过VI型分泌系统提供多态性抗菌毒素。这种毒素以NAD+依赖性方式抑制蛋白质合成。使用NAD的生物素化衍生物,我们证明了通过核糖体23S RNA的ADP-核糖基化抑制翻译。修饰的映射进一步表明,加合物位于位于GTPa​​se相关中心的硫代膜环的螺旋44上,并降低了EF-G延伸因子的GTPase活性。 Laumondii Photorhabdus Laumondii使用其VI型分泌系统(T6SS)提供了一种与RHS连接的毒素,该毒素可将目标细胞中的23S核糖体RNA ADP核糖基化,以阻止翻译。
Bacteria have evolved sophisticated mechanisms to deliver potent toxins into bacterial competitors or into eukaryotic cells in order to destroy rivals and gain access to a specific niche or to hijack essential metabolic or signaling pathways in the host. Delivered effectors carry various activities such as nucleases, phospholipases, peptidoglycan hydrolases, enzymes that deplete the pools of NADH or ATP, compromise the cell division machinery, or the host cell cytoskeleton. Effectors categorized in the family of polymorphic toxins have a modular structure, in which the toxin domain is fused to additional elements acting as cargo to adapt the effector to a specific secretion machinery. Here we show that Photorhabdus laumondii, an entomopathogen species, delivers a polymorphic antibacterial toxin via a type VI secretion system. This toxin inhibits protein synthesis in a NAD+-dependent manner. Using a biotinylated derivative of NAD, we demonstrate that translation is inhibited through ADP-ribosylation of the ribosomal 23S RNA. Mapping of the modification further showed that the adduct locates on helix 44 of the thiostrepton loop located in the GTPase-associated center and decreases the GTPase activity of the EF-G elongation factor. Photorhabdus laumondii uses its type VI secretion system (T6SS) to deliver a Rhs-linked toxin that ADP-ribosylates the 23S ribosomal RNA in the target bacterial cell to arrest translation.
DOI: 10.1371/journal.ppat.1005735
发表时间: 2016-06
期刊: PLoS pathogens
影响因子: 6.7
作者:
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通讯作者: Coulthurst SJ
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