An X-Domain Phosphoinositide Phospholipase C (PI-PLC-like) of Trypanosoma brucei Has a Surface Localization and Is Essential for Proliferation.
An X-Domain Phosphoinositide Phospholipase C (PI-PLC-like) of Trypanosoma brucei Has a Surface Localization and Is Essential for Proliferation.
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DOI：
10.3390/pathogens12030386
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发表时间：
2023-02-28
期刊：
影响因子：
--
通讯作者：
Docampo R
中科院分区：
文献类型：
--
作者：
Negrão NW;Crowe LP;Mantilla BS;Baptista RP;King-Keller S;Huang G;Docampo R
布鲁氏锥虫是非洲锥虫病的病原体，非洲锥虫病是一种影响人类和牛的致命疾病。治疗它的药物很少，而且有证据表明耐药性正在增加，这增加了开发新药的必要性。在这里，我们报道了一种磷酸肌苷磷脂酶C （tbpi - plc样）的存在，它含有一个X和一个PDZ结构域，与之前表征的TbPI-PLC1相似。TbPI-PLC-like只具有X催化结构域，不具有EF-hand， Y和C2结构域，而是具有PDZ结构域。重组TbPI-PLC-like不水解磷脂酰肌醇4,5-二磷酸（PIP2），也不调节TbPI-PLC1的活性。tbpi - plc样蛋白在通透性细胞中表现为质膜和细胞内定位，在非通透性细胞中表现为表面定位。令人惊讶的是，通过RNAi敲低tbpi - plc样表达显著影响原环和血流锥乳线虫的增殖。这与下调TbPI-PLC1表达缺乏效果形成对比。
Trypanosoma brucei is the causative agent of African trypanosomiasis, a deadly disease that affects humans and cattle. There are very few drugs to treat it, and there is evidence of mounting resistance, raising the need for new drug development. Here, we report the presence of a phosphoinositide phospholipase C (TbPI-PLC-like), containing an X and a PDZ domain, that is similar to the previously characterized TbPI-PLC1. TbPI-PLC-like only possesses the X catalytic domain and does not have the EF-hand, Y, and C2 domains, having instead a PDZ domain. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity in vitro. TbPI-PLC-like shows a plasma membrane and intracellular localization in permeabilized cells and a surface localization in non-permeabilized cells. Surprisingly, knockdown of TbPI-PLC-like expression by RNAi significantly affected proliferation of both procyclic and bloodstream trypomastigotes. This is in contrast with the lack of effect of downregulation of expression of TbPI-PLC1.
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影响因子：
56.9
作者：
FERGUSON, MAJ;HOMANS, SW;RADEMACHER, TW
通讯作者：
RADEMACHER, TW
影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
从细菌到人类细胞的细胞器保守的酸性蛋白质组学分析。
影响因子：
6.7
作者：
Huang G;Ulrich PN;Storey M;Johnson D;Tischer J;Tovar JA;Moreno SN;Orlando R;Docampo R
通讯作者：
Docampo R
影响因子：
64.8
作者：
DEALMEIDA, MLC;TURNER, MJ
通讯作者：
TURNER, MJ
影响因子：
4.8
作者：
Furuya, T;Kashuba, C;Moreno, SNJ
通讯作者：
Moreno, SNJ