Jewett Travis J, Fischer Elizabeth R, Mead David J, Hackstadt Ted
Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15599-604. doi: 10.1073/pnas.0603044103. Epub 2006 Oct 6.
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.
沙眼衣原体进入宿主细胞是由寄生虫引导的肌动蛋白细胞骨架重塑所致。一种III型分泌效应蛋白TARP（转运肌动蛋白募集磷蛋白）与肌动蛋白募集至内化位点有关。为阐明TARP在肌动蛋白募集中的作用，我们鉴定了与重组GST-TARP融合蛋白相关的宿主细胞蛋白。TARP直接与肌动蛋白结合，且这种相互作用促进了肌动蛋白成核，这是通过体外聚合试验确定的。对TARP的结构域分析鉴定出一个肌动蛋白结合结构域，该结构域在结构和一级氨基酸序列上与WH2结构域家族蛋白相似。此外，发现一个富含脯氨酸的结构域可促进TARP寡聚化，且是TARP依赖的新肌动蛋白丝成核所必需的。我们的研究结果揭示了一种机制，即衣原体在进入宿主细胞过程中通过转运效应蛋白TARP诱导局部细胞骨架变化。
