To create an intracellular niche permissive for its replication, Legionella pneumophila uses hundreds of effectors to target a wide variety of host proteins and manipulate specific host processes such as immune response, and vesicle trafficking. To avoid unwanted disruption of host physiology, this pathogen also imposes precise control of its virulence by the use of effectors called metaeffectors to regulate the activity of other effectors. A number of effector/metaeffector pairs with distinct regulatory mechanisms have been characterized, including abrogation of protein modifications, direct modification of the effector and direct binding to the catalytic pocket of the cognate effector. Recently, MesI (Lpg2505) was found to be a metaeffector of SidI, an effector involved in inhibiting host protein translation. Here we demonstrate that MesI functions by inhibiting the activity of SidI via direct protein–protein interactions. We show that this interaction occurs within L. pneumophila and thus interferes with the translocation of SidI into host cells. We also solved the structure of MesI, which suggests that this protein does not have an active site similar to any known enzymes. Analysis of deletion mutants allowed the identification of regions within SidI and MesI that are important for their interactions.

为了创造一个允许其复制的细胞内生态位，嗜肺军团菌使用数百个效应器来靶向多种宿主蛋白​​并操纵特定的宿主过程，例如免疫反应和囊泡运输。为了避免对宿主生理造成不必要的破坏，这种病原体还通过使用称为元效应器的效应器来调节其他效应器的活性，从而对其毒力进行精确控制。已经表征了许多具有不同调节机制的效应器/元效应器对，包括取消蛋白质修饰、直接修饰效应器和直接结合同源效应器的催化袋。最近，发现 MesI (Lpg2505) 是 SidI 的元效应器，SidI 是一种参与抑制宿主蛋白翻译的效应器。在这里，我们证明 MesI 通过直接的蛋白质-蛋白质相互作用抑制 SidI 的活性来发挥作用。L. pneumophila 从而干扰 SidI 易位到宿主细胞中。我们还解决了 MesI 的结构，这表明该蛋白质不具有与任何已知酶相似的活性位点。对缺失突变体的分析允许识别对它们的相互作用很重要的 SidI 和 MesI 内的区域。