Legionella RavZ Plays a Role in Preventing Ubiquitin Recruitment to Bacteria-Containing Vacuoles.

Legionella RavZ Plays a Role in Preventing Ubiquitin Recruitment to Bacteria-Containing Vacuoles.
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DOI:
10.3389/fcimb.2017.00384
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发表时间:
2017
影响因子:
5.7
通讯作者:
Nagai H
Nagai H
中科院分区:
医学2区
文献类型:
--
作者:
Kubori T;Bui XT;Hubber A;Nagai H

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像沙门氏菌和军团菌这样的细菌病原体在宿主细胞中建立细胞内的壁龛,称为含细菌液泡。在这些液泡中,细菌可以生存和复制。泛素依赖的选择性自噬是宿主抵抗入侵病原体感染的一种防御机制。军团菌效应蛋白RavZ通过不可逆地从磷酸糖脂磷脂酰乙醇胺中解耦LC3(一种与自噬相关的泛素样蛋白)来干扰自噬。使用与沙门氏菌共感染系统,我们在这里显示军团菌RavZ干扰泛素募集到含沙门氏菌液泡。抑制活性依赖于参与LC3解偶联的RavZ的相同催化残基。在感染沙门氏菌的半透性细胞中,外部添加纯化的RavZ蛋白,而不是其催化突变体,诱导了与含沙门氏菌液泡相关的泛素的去除。在没有LC3结合所需的宿主系统的情况下,ravz介导的泛素募集到含沙门氏菌液泡的限制发生了。这些观察结果表明,RavZ解偶联活性的靶点可能不仅包括LC3,还包括泛素。
Bacterial pathogens like Salmonella and Legionella establish intracellular niches in host cells known as bacteria-containing vacuoles. In these vacuoles, bacteria can survive and replicate. Ubiquitin-dependent selective autophagy is a host defense mechanism to counteract infection by invading pathogens. The Legionella effector protein RavZ interferes with autophagy by irreversibly deconjugating LC3, an autophagy-related ubiquitin-like protein, from a phosphoglycolipid phosphatidylethanolamine. Using a co-infection system with Salmonella, we show here that Legionella RavZ interferes with ubiquitin recruitment to the Salmonella-containing vacuoles. The inhibitory activity is dependent on the same catalytic residue of RavZ that is involved in LC3 deconjugation. In semi-permeabilized cells infected with Salmonella, external addition of purified RavZ protein, but not of its catalytic mutant, induced removal of ubiquitin associated with Salmonella-containing vacuoles. The RavZ-mediated restriction of ubiquitin recruitment to Salmonella-containing vacuoles took place in the absence of the host system required for LC3 conjugation. These observations suggest the possibility that the targets of RavZ deconjugation activity include not only LC3, but also ubiquitin.
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