A Salmonella typhimurium effector protein SifA is modified by host cell prenylation and S-acylation machinery
A Salmonella typhimurium effector protein SifA is modified by host cell prenylation and S-acylation machinery
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DOI：
10.1074/jbc.m500076200
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发表时间：
2005-04-15
影响因子：
4.8
通讯作者：
Kelly, AP
中科院分区：
文献类型：
--
作者：
Reinicke, AT;Hutchinson, JL;Kelly, AP
SifA是一种沙门氏菌效应蛋白，是维持围绕复制细菌的空泡膜所必需的。它与含有沙门氏菌的液泡有关，但它如何与膜相互作用尚不清楚。本研究通过免疫荧光、S100分离和Triton X-114分割表明，SifA的膜结合和靶向特性受到c端6个氨基酸编码的基序的影响。该序列与CAAX和Rab香叶基香叶基转移酶戊酰化基序具有同源性。我们对SifA的翻译后加工进行了表征，并表明CAAX基序内的半胱氨酸残基是通过蛋白香叶基转移酶i的类异戊二烯添加进行修饰的。宿主细胞蛋白的类似修饰调节多种功能，包括蛋白靶向、膜结合、蛋白-蛋白相互作用和信号转导。这是唯一已知的细菌效应蛋白被哺乳动物细胞s -酰化和戊酰化机制修饰的例子。
SifA is a Salmonella effector protein that is required for maintenance of the vacuolar membrane that surrounds replicating bacteria. It associates with the Salmonella-containing vacuole but how it interacts with the membrane is unknown. Here we show by immunofluorescence, S100 fractionation and Triton X-114 partitioning that the membrane association and targeting properties of SifA are influenced by a motif encoded within the C-terminal six amino acids. This sequence shares homology with both CAAX and Rab geranylgeranyl transferase prenylation motifs. We characterized the post-translational processing of SifA and showed that the cysteine residue within the CAAX motif is modified by isoprenoid addition through the action of protein geranylgeranyl transferase I. SifA was additionally modified by S-acylation of an adjacent cysteine residue. Similar modifications to host cell proteins regulate numerous functions including protein targeting, membrane association, protein-protein interaction, and signal transduction. This is the only known example of a bacterial effector protein that is modified both by mammalian cell S-acylation and prenylation machinery.