Structure of a bacterial Rhs effector exported by the type VI secretion system.
Structure of a bacterial Rhs effector exported by the type VI secretion system.
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DOI：
10.1371/journal.ppat.1010182
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发表时间：
2022-01
期刊：
影响因子：
6.7
通讯作者：
Raunser S
中科院分区：
文献类型：
--
作者：
Günther P;Quentin D;Ahmad S;Sachar K;Gatsogiannis C;Whitney JC;Raunser S
VI型分泌系统（T6 SS）是在革兰氏阴性菌中发现的广泛的蛋白质输出装置。大多数T6 SS将毒性效应蛋白递送到竞争细菌中。然而，许多这些效应物的结构、功能和激活仍然知之甚少。在这里，我们提出的结构T6 SS效应RhsA从假单胞菌及其同源T6 SS刺突蛋白，VgrG 1，在3.3 μ m分辨率。结构表明，RhsA的重排热点（Rhs）重复组装成一个封闭的反式β-桶螺旋，类似于在细菌杀虫Tc毒素和后生动物teneurin蛋白中发现的。我们发现，RhsA的C-末端毒素结构域是autoproteolytically裂解，但仍然在Rhs的“茧”，其中，除了三个有序的结构元素，大部分的毒素是无序的。N-末端“塞子”结构域是T6 SS Rhs蛋白所特有的，类似于香槟软木塞，其在一端密封Rhs茧，同时还介导与VgrG 1的相互作用。有趣的是，这个结构域也autoproteolytically切割内的茧，但仍然与it. We建议，机械力是需要删除的插头切割的部分，导致在释放的毒素结构域，因为它是由T6 SS传递到一个敏感的细菌细胞。细菌已经发展出各种各样的策略来竞争营养和有限的资源。革兰氏阴性细菌广泛使用的一种系统是T6分泌系统，其将过多的效应物递送到竞争细菌细胞中。效应子的已知功能是细胞壁的降解、必需代谢物如NAD+的消耗或DNA的切割。RhsA是来自广泛的植物保护细菌假单胞菌的效应子。我们发现，RhsA形成一个封闭的茧中发现的细菌Tc毒素和后生动物teneurin蛋白类似。该效应物自身将其多肽链切割成三部分，即包括密封物的N-末端结构域、茧和潜在切割DNA的实际毒性组分。有毒成分被封装在大茧中，从而保护产生效应物的细菌免受毒素的影响。为了使毒素退出茧，我们建议，密封，关闭茧的一端，被删除的机械力期间注射的效应T6分泌系统。我们进一步假设了将毒素递送到宿主细胞的细胞质中的不同情况。总之，我们的研究结果扩展了T6分泌系统的作用机制及其在细菌间竞争中的重要作用的知识。
The type VI secretion system (T6SS) is a widespread protein export apparatus found in Gram-negative bacteria. The majority of T6SSs deliver toxic effector proteins into competitor bacteria. Yet, the structure, function, and activation of many of these effectors remains poorly understood. Here, we present the structures of the T6SS effector RhsA from Pseudomonas protegens and its cognate T6SS spike protein, VgrG1, at 3.3 Å resolution. The structures reveal that the rearrangement hotspot (Rhs) repeats of RhsA assemble into a closed anticlockwise β-barrel spiral similar to that found in bacterial insecticidal Tc toxins and in metazoan teneurin proteins. We find that the C-terminal toxin domain of RhsA is autoproteolytically cleaved but remains inside the Rhs ‘cocoon’ where, with the exception of three ordered structural elements, most of the toxin is disordered. The N-terminal ‘plug’ domain is unique to T6SS Rhs proteins and resembles a champagne cork that seals the Rhs cocoon at one end while also mediating interactions with VgrG1. Interestingly, this domain is also autoproteolytically cleaved inside the cocoon but remains associated with it. We propose that mechanical force is required to remove the cleaved part of the plug, resulting in the release of the toxin domain as it is delivered into a susceptible bacterial cell by the T6SS. Bacteria have developed a variety of strategies to compete for nutrients and limited resources. One system widely used by Gram-negative bacteria is the T6 secretion system which delivers a plethora of effectors into competing bacterial cells. Known functions of effectors are degradation of the cell wall, the depletion of essential metabolites such as NAD+ or the cleavage of DNA. RhsA is an effector from the widespread plant-protecting bacteria Pseudomonas protegens. We found that RhsA forms a closed cocoon similar to that found in bacterial Tc toxins and metazoan teneurin proteins. The effector cleaves its polypeptide chain by itself in three pieces, namely the N-terminal domain including a seal, the cocoon and the actual toxic component which potentially cleaves DNA. The toxic component is encapsulated in the large cocoon, so that the effector producing bacterium is protected from the toxin. In order for the toxin to exit the cocoon, we propose that the seal, which closes the cocoon at one end, is removed by mechanical forces during injection of the effector by the T6 secretion system. We further hypothesize about different scenarios for the delivery of the toxin into the cytoplasm of the host cell. Together, our findings expand the knowledge of the mechanism of action of the T6 secretion system and its essential role in interbacterial competition.
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