Host-mediated post-translational prenylation of novel dot/icm-translocated effectors of legionella pneumophila.
Host-mediated post-translational prenylation of novel dot/icm-translocated effectors of legionella pneumophila.
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DOI：
10.3389/fmicb.2010.00131
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发表时间：
2010
影响因子：
5.2
通讯作者：
Kwaik YA
中科院分区：
文献类型：
--
作者：
Price CT;Jones SC;Amundson KE;Kwaik YA
嗜肺军团菌的 Dot/Icm IV 型易位锚蛋白 B (AnkB) 效应器通过宿主异戊二烯化机制进行修饰，将其锚定到含军团菌液泡 (LCV) 的外叶中，这对于效应器的体外和体内生物学功能至关重要。异戊二烯化涉及类异戊二烯脂质部分与真核蛋白中 C 端 CaaX 基序的共价连接，使其能够锚定到膜上。我们在此表明，携带 ankB 无效突变体的 LCV 以 Dot/Icm 依赖性方式用异戊二烯化蛋白装饰，表明其他 LCV 膜锚定蛋白也被异戊二烯化。对四个已测序的嗜肺军团菌基因组进行的计算机分析揭示了其他 11 个基因的存在，这些基因编码具有 C 端真核 CaaX 异戊二烯化基序的蛋白质。在这 11 个指定的军团菌 (Pel) 异戊二烯化效应子中，有 7 个也在嗜肺军团菌 AA100 中发现。我们发现，六种嗜肺军团菌 AA100 Pel 蛋白在哺乳动物细胞中异位表达时表现出不同的细胞定位，这取决于宿主异戊二烯化机制的作用和 CaaX 基序的保守半胱氨酸残基。尽管抑制宿主异戊二烯化机制完全阻止了嗜肺军团菌的液泡内增殖，但它对 LCV 的细胞内运输仅具有适度的影响。其中五种 Pel 蛋白通过嗜肺军团菌的 Dot/Icm IV 型易位系统注射到人巨噬细胞中。总的来说，Pel 蛋白是嗜肺军团菌新型 Dot/Icm 易位效应子，通过宿主异戊二烯化机制进行翻译后修饰，使其能够锚定到细胞膜中，并且异戊二烯化效应子有助于 LCV 逃避溶酶体融合。
The Dot/Icm type IV translocated Ankyrin B (AnkB) effector of Legionella pneumophila is modified by the host prenylation machinery that anchors it into the outer leaflet of the Legionella-containing vacuole (LCV), which is essential for biological function of the effector in vitro and in vivo. Prenylation involves the covalent linkage of an isoprenoid lipid moiety to a C-terminal CaaX motif in eukaryotic proteins enabling their anchoring into membranes. We show here that the LCV harboring an ankB null mutant is decorated with prenylated proteins in a Dot/Icm-dependent manner, indicating that other LCV membrane-anchored proteins are prenylated. In silico analyses of four sequenced L. pneumophila genomes revealed the presence of eleven other genes that encode proteins with a C-terminal eukaryotic CaaX prenylation motif. Of these eleven designated Prenylated effectors of Legionella (Pel), seven are also found in L. pneumophila AA100. We show that six L. pneumophila AA100 Pel proteins exhibit distinct cellular localization when ectopically expressed in mammalian cells and this is dependent on action of the host prenylation machinery and the conserved cysteine residue of the CaaX motif. Although inhibition of the host prenylation machinery completely blocks intra-vacuolar proliferation of L. pneumophila, it only had a modest effect on intracellular trafficking of the LCV. Five of the Pel proteins are injected into human macrophages by the Dot/Icm type IV translocation system of L. pneumophila. Taken together, the Pel proteins are novel Dot/Icm-translocated effectors of L. pneumophila that are post-translationally modified by the host prenylation machinery, which enables their anchoring into cellular membranes, and the prenylated effectors contribute to evasion of lysosomal fusion by the LCV.
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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：
3.4
作者：
Lomma, M.;Dervins-Ravault, D.;Buchrieser, C.
通讯作者：
Buchrieser, C.
细菌效应器设计和功能的常见主题。
影响因子：
30.3
作者：
Galan, Jorge E.
通讯作者：
Galan, Jorge E.