Lysine11-Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila
Lysine11-Linked Polyubiquitination of the AnkB F-Box Effector of Legionella pneumophila
复制标题
DOI：
10.1128/iai.01165-15
复制
发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Abu Kwaik, Yousef
中科院分区：
文献类型：
--
作者：
Bruckert, William M.;Abu Kwaik, Yousef
多聚泛素化蛋白的命运由参与泛素单体聚合的赖氨酸键决定，其具有七个赖氨酸残基（K-6、K-11、K-27、K-29、K-33、K-48和K-63）。空泡内病原体嗜肺军团菌的易位AnkB效应子是真正的F盒蛋白，其定位于含军团菌空泡（LCV）的胞质侧，并且对于巨噬细胞和阿米巴内的空泡内增殖是必需的。AnkB的F-box结构域与宿主SCF 1 E3泛素连接酶相互作用，引发LCV被靶向蛋白酶体降解的K-48连接的多聚泛素化蛋白修饰。在这里，我们报告说，AnkB成为迅速多泛素化的宿主细胞内，这种修饰是独立的F-box结构域的AnkB，表明主机介导的多泛素化。我们发现AnkB效应器与宿主E3泛素连接酶Trim 21特异性相互作用。质谱分析表明，AnkB被K-11连接的多聚泛素化修饰，这对其稳定性没有影响。这项工作显示了K-11连接的细菌效应子的多泛素化及其与宿主Trim 21泛素连接酶的相互作用的第一个例子。
The fate of the polyubiquitinated protein is determined by the lysine linkages involved in the polymerization of the ubiquitin monomers, which has seven lysine residues (K-6, K-11, K-27, K-29, K-33, K-48, and K-63). The translocated AnkB effector of the intravacuolar pathogen Legionella pneumophila is a bona fide F-box protein, which is localized to the cytosolic side of the Legionella-containing vacuole (LCV) and is essential for intravacuolar proliferation within macrophages and amoebae. The F-box domain of AnkB interacts with the host SCF1 E3 ubiquitin ligase that triggers the decoration of the LCV with K-48-linked polyubiquitinated proteins that are targeted for proteasomal degradation. Here we report that AnkB becomes rapidly polyubiquitinated within the host cell, and this modification is independent of the F-box domain of AnkB, indicating host-mediated polyubiquitination. We show that the AnkB effector interacts specifically with the host E3 ubiquitin ligase Trim21. Mass spectrometry analyses have shown that AnkB is modified by K-11-linked polyubiquitination, which has no effect on its stability. This work shows the first example of K-11-linked polyubiquitination of a bacterial effector and its interaction with the host Trim21 ubiquitin ligase.