Chlamydial TARP is a bacterial nucleator of actin
Chlamydial TARP is a bacterial nucleator of actin
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DOI：
10.1073/pnas.0603044103
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发表时间：
2006-10-17
影响因子：
11.1
通讯作者：
Hackstadt, Ted
中科院分区：
文献类型：
--
作者：
Jewett, Travis J.;Fischer, Elizabeth R.;Hackstadt, Ted
沙眼衣原体进入宿主细胞是由寄生虫定向的肌动蛋白细胞骨架重塑所致。 III 型分泌效应子 TARP（易位肌动蛋白募集磷蛋白）与肌动蛋白募集到内化位点有关。为了阐明 TARP 在肌动蛋白募集中的作用，我们鉴定了与重组 GST-TARP 融合相关的宿主细胞蛋白。 TARP 与肌动蛋白直接相关，并且根据体外聚合测定确定，这种相互作用促进了肌动蛋白成核。 TARP 的结构域分析鉴定出一个肌动蛋白结合结构域，其结构和一级氨基酸序列与 WH2 结构域家族蛋白相似。此外，还发现富含脯氨酸的结构域可以促进 TARP 寡聚化，并且是新肌动蛋白丝的 TARP 依赖性成核所必需的。我们的研究结果揭示了衣原体在进入宿主细胞期间通过易位效应器 TARP 诱导局部细胞骨架变化的机制。
Chlamydia trachomatis entry into host cells results from a parasite-directed remodeling of the actin cytoskeleton. A type III secreted effector, TARP (translocated actin recruiting phosphoprotein), has been implicated in the recruitment of actin to the site of internalization. To elucidate the role of TARP in actin recruitment, we identified host cell proteins that associated with recombinant GST-TARP fusions. TARP directly associated with actin, and this interaction promoted actin nucleation as determined by in vitro polymerization assays. Domain analysis of TARP identified an actin-binding domain that bears structural and primary amino acid sequence similarity to WH2 domain family proteins. In addition, a proline-rich domain was found to promote TARP oligomerization and was required for TARP-dependent nucleation of new actin filaments. Our findings reveal a mechanism by which chlamydiae induce localized cytoskeletal changes by the translocated effector TARP during entry into host cells.