Kielkopf Claudia S, Shneider Mikhail M, Leiman Petr G, Taylor Nicholas M I
Structural Biology of Molecular Machines Group, Protein Structure & Function Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Molecular Bioengineering, 16/10 Miklukho-Maklaya Street, 117997 Moscow, Russia; École Polytechnique Fédérale de Lausanne (EPFL), BSP-415, 1015 Lausanne, Switzerland.
Structure. 2024 Dec 5;32(12):2375-2389.e5. doi: 10.1016/j.str.2024.10.008. Epub 2024 Oct 30.
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.
细菌利用VI型分泌系统（T6SS），通过由收缩鞘和刚性管组成的机制，将毒素分泌到原核细胞和真核细胞中。重排热点（Rhs）蛋白是最常见的T6SS效应蛋白之一。Rhs C端毒素结构域具有很大的功能多样性，而Rhs核心以YD重复序列为特征。我们分别阐明了来自邦戈沙门氏菌和米氏艾文氏菌的与PAAR和VgrG相关的Rhs蛋白的Rhs核心结构。Rhs核心形成了一个由β折叠组成的大外壳，内部带负电荷，并包围着一个大的空间。邦戈沙门氏菌的Rhs毒素在Rhs外壳中不会形成有序的密度，这表明该毒素是未折叠的。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，既是产生毒素的细胞的安全特征，又是毒素的递送机制。
