Bacteria use the type VI secretion system (T6SS) to secrete toxins into pro- and eukaryotic cells via machinery consisting of a contractile sheath and a rigid tube. Rearrangement hotspot (Rhs) proteins represent one of the most common T6SS effectors. The Rhs C-terminal toxin domain displays great functional diversity, while the Rhs core is characterized by YD repeats. We elucidate the Rhs core structures of PAAR- and VgrG-linked Rhs proteins from Salmonella bongori and Advenella mimigardefordensis, respectively. The Rhs core forms a large shell of β-sheets with a negatively charged interior and encloses a large volume. The S. bongori Rhs toxin does not lead to ordered density in the Rhs shell, suggesting the toxin is unfolded. Together with bioinformatics analysis showing that Rhs toxins predominantly act intracellularly, this suggests that the Rhs core functions two-fold, as a safety feature for the producer cell and as delivery mechanism for the toxin.

中文翻译：

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T6SS 相关 Rhs 毒素包封壳：对细菌武器和自我保护的结构和生物信息学见解


细菌使用 VI 型分泌系统 （T6SS） 通过由收缩鞘和硬管组成的机制将毒素分泌到促核细胞和真核细胞中。重排热点 （Rhs） 蛋白是最常见的 T6SS 效应子之一。Rhs C 末端毒素结构域表现出极大的功能多样性，而 Rhs 核心以 YD 重复序列为特征。我们阐明了分别来自 Salmonella bongori 和 Advenella mimigardefordensis 的 PAAR 和 VgrG 连接的 Rhs 蛋白的 Rhs 核心结构。Rhs 芯形成一个大的 β 片壳，内部带负电，并包围着一个大体积。S. bongori Rhs 毒素不会导致 Rhs 壳中有序密度，这表明毒素已展开。结合生物信息学分析表明 Rhs 毒素主要在细胞内起作用，这表明 Rhs 核心具有双重功能，作为生产细胞的安全特征和毒素的递送机制。