Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Nat Commun. 2024 Aug 30;15(1):7481. doi: 10.1038/s41467-024-51273-1.
Ubiquitination is a posttranslational modification in eukaryotes that plays a significant role in the infection of intracellular microbial pathogens, such as Legionella pneumophila. While the Legionella-containing vacuole (LCV) is coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report that the Sdc and Sde families of effectors work together to build ubiquitinated species around the LCV. The Sdc effectors catalyze canonical polyubiquitination directly on host targets or on phosphoribosyl-Ub conjugated to host targets by Sde. Remarkably, Ub moieties within poly-Ub chains are either modified with a phosphoribosyl group by PDE domain-containing effectors or covalently attached to other host substrates via Sde-mediated phosphoribosyl-ubiquitination. Furthermore, these modifications prevent the recognition by Ub adaptors and therefore exclude host autophagy adaptors from the LCV. In this work, we shed light on the nature of the poly-ubiquitinated species present at the surface of the LCV and provide a molecular mechanism for the avoidance of autophagy adaptors by the Ub-decorated LCV.
泛素化是真核生物中的一种翻译后修饰，在细胞内微生物病原体（如嗜肺军团菌）的感染中起着重要作用。虽然含有军团菌的空泡（LCV）被泛素（Ub）覆盖，但它可以避免被自噬衔接蛋白识别。在这里，我们报告说效应物 Sdc 和 Sde 家族共同作用，在 LCV 周围构建泛素化的物质。Sdc 效应物直接在宿主靶标上或 Sde 连接到宿主靶标上的磷酸核糖基-Ub 上催化典型的多泛素化。值得注意的是，多泛素链内的 Ub 部分要么由含有 PDE 结构域的效应物修饰为磷酸核糖基，要么通过 Sde 介导的磷酸核糖基泛素化共价连接到其他宿主底物上。此外，这些修饰阻止了 Ub 衔接蛋白的识别，从而使宿主自噬衔接蛋白不能识别 LCV。在这项工作中，我们阐明了 LCV 表面存在的多泛素化物质的性质，并提供了一个分子机制，解释了 Ub 修饰的 LCV 如何避免被自噬衔接蛋白识别。
