Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila.
Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila.
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DOI：
10.1084/jem.20100771
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发表时间：
2010-08-02
期刊：
影响因子：
--
通讯作者：
Abu Kwaik Y
中科院分区：
文献类型：
--
作者：
Price CT;Al-Quadan T;Santic M;Jones SC;Abu Kwaik Y
法尼基化涉及真核生物蛋白质与脂质部分的共价连接以将它们锚入膜中，这对于Ras和其他蛋白质的生物学功能是必需的。一个大干部的细菌效应器注入宿主细胞的液泡内病原体通过精心制作的III-VII型易位机制，这些效应器中的许多被纳入到病原体含有液泡膜的未知机制。嗜肺军团菌的Dot/Icm IV型分泌系统将F-盒效应物锚蛋白B（Ank B）注入宿主细胞，其作为多泛素化蛋白与含军团菌的空泡（LCV）对接的平台，以使巨噬细胞和阿米巴中的空泡内增殖成为可能。我们发现，AnkB的法尼基化是必不可少的锚定到LCV膜的胞质面，其在巨噬细胞和Dictyosteelium discoideum内的生物学功能，并在小鼠肺内增殖。值得注意的是，蛋白质法尼基转移酶，RCE-1（Ras-转化酶-1），和异戊二烯基半胱氨酸羧基甲基转移酶宿主法尼基化酶被招募到LCV在一个点/Icm依赖性的方式，是必不可少的AnkB的生物功能。总之，本研究显示了新的本地招聘的主机法尼基化机器和锚定的F-盒效应LCV膜，这是必不可少的生物功能在体外和体内。
Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.
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影响因子：
15.9
作者：
Al-Khodor S;Price CT;Kalia A;Abu Kwaik Y
通讯作者：
Abu Kwaik Y
影响因子：
4.8
作者：
Boucrot, E;Beuzón, CR;Méresse, S
通讯作者：
Méresse, S
影响因子：
3.3
作者：
Al-Khodor, Souhaila;Al-Quadan, Tasneem;Abu Kwaik, Yousef
通讯作者：
Abu Kwaik, Yousef
影响因子：
6.7
作者：
Price CT;Al-Khodor S;Al-Quadan T;Santic M;Habyarimana F;Kalia A;Kwaik YA
通讯作者：
Kwaik YA
影响因子：
4.8
作者：
LERNER, EC;QIAN, YM;SEBTI, SM
通讯作者：
SEBTI, SM