The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice.
The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice.
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DOI：
10.1016/j.chom.2014.04.002
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发表时间：
2014-05-14
影响因子：
30.3
通讯作者：
Sibley LD
中科院分区：
文献类型：
--
作者：
Etheridge RD;Alaganan A;Tang K;Lou HJ;Turk BE;Sibley LD
弓形虫杆状体分泌型多型激酶（Polymorphic rhoptry secreted kinases，ROP）是弓形虫的重要毒力因子。特别是，假激酶ROP 5是小鼠急性毒力的主要决定因素，但其潜在机制尚不清楚。本研究建立了T.并用它来显示ROP 5与活性激酶ROP 18和ROP 17复合。生化分析表明，ROP18和ROP17已进化为靶向免疫相关GTP酶（IRGs）开关区I中相邻的和必需的苏氨酸残基，IRGs是一个具有控制胞内病原体功能的宿主防御分子家族。ROP 17和ROP 18的组合活性有助于避免IRG募集到细胞内T细胞。从而保护寄生虫免受干扰素活化的巨噬细胞的清除。这些研究揭示了一个复杂的，多层次的寄生虫生存策略，涉及假激酶，调节多个活性激酶复合物，协同阻碍先天免疫。
Polymorphic rhoptry secreted kinases (ROPs) are essential virulence factors of Toxoplasma gondii. In particular, the pseudokinase ROP5 is the major determinant of acute virulence in mice, but the underlying mechanisms are unclear. We developed a tandem affinity protein tagging and purification approach in T. gondii and used it to show that ROP5 complexes with the active kinases ROP18 and ROP17. Biochemical analyses indicates that ROP18 and ROP17 have evolved to target adjacent and essential threonine residues in switch region I of immunity related GTPases (IRGs), a family of host defense molecules that function to control of intracellular pathogens. The combined activities of ROP17 and ROP18 contribute to avoidance of IRG recruitment to the intracellular T. gondii containing vacuole, thus protecting the parasite from clearance in interferon-activated macrophages. These studies reveal an intricate, multi-layered parasite survival strategy involving pseudokinases that regulate multiple active kinase complexes to synergistically thwart innate immunity.
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影响因子：
3.4
作者：
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通讯作者：
Sibley LD