A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication.
A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication.
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DOI：
10.1016/j.chom.2016.12.007
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发表时间：
2017-02-08
影响因子：
30.3
通讯作者：
Isberg RR
中科院分区：
文献类型：
--
作者：
Kotewicz KM;Ramabhadran V;Sjoblom N;Vogel JP;Haenssler E;Zhang M;Behringer J;Scheck RA;Isberg RR
细胞内病原体操纵宿主细胞器以支持细胞内的复制。对于嗜肺军团菌，细菌易位蛋白质，建立内质网（ER）相关的复制区室。我们在这里表明，细菌Sde蛋白靶向宿主reticulon 4（Rtn 4）控制肾小管ER动力学，导致肾小管重排以及与复制室相关的Rtn 4的改变。这些重排是通过Sde促进的泛素转移到Rtn 4而触发的，几乎在细菌摄取后立即发生。泛素转移需要来自单个Sde多肽的两个连续的酶活性：ADP-核糖基转移酶和核苷酸酶/磷酸水解酶。泛素的ADP-核糖基化部分是核苷酸酶/磷酸水解酶的底物，导致泛素转移到Rtn 4，或在不存在泛素化靶点的情况下泛素的磷酸核糖基化。因此，一个单一的细菌蛋白驱动一个多步骤的生化途径，以控制泛素化和管状ER功能独立的主机泛素机制。
Intracellular pathogens manipulate host organelles to support replication within cells. For Legionella pneumophila, the bacterium translocates proteins that establish an endoplasmic reticulum (ER)-associated replication compartment. We show here that the bacterial Sde proteins target host reticulon 4 (Rtn4) to control tubular ER dynamics, resulting in tubule rearrangements as well as alterations in Rtn4 associated with the replication compartment. These rearrangements are triggered via Sde-promoted ubiquitin transfer to Rtn4, occurring almost immediately after bacterial uptake. Ubiquitin transfer requires two sequential enzymatic activities from a single Sde polypeptide: an ADP-ribosyltransferase and a nucleotidase/phosphohydrolase. The ADP-ribosylated moiety of ubiquitin is a substrate for the nucleotidase/phosphohydrolase, resulting in either transfer of ubiquitin to Rtn4, or phosphoribosylation of ubiquitin in the absence of a ubiquitination target. Therefore, a single bacterial protein drives a multistep biochemical pathway to control ubiquitination and tubular ER function independently of the host ubiquitin machinery.