Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest
Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest
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DOI：
10.1007/s12192-015-0595-y
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发表时间：
2015-07-01
影响因子：
3.8
通讯作者：
Clos, Joachim
中科院分区：
文献类型：
--
作者：
Hombach, Antje;Ommen, Gabi;Clos, Joachim
在杜氏利什曼原虫中，HSP90伴侣复合体在控制寄生虫的生命周期、一般生存能力和传染性方面起着至关重要的作用。一些相关的辅助伴侣也被证明对哺乳动物细胞的活性和/或感染性是必不可少的。在这里，我们鉴定和描述了辅助伴侣P23，并将其功能与结构上相关的小分子热休克蛋白HSP23区分开来。P23是结构性表达的，并与HSP90复合体的成员，即HSP90和STI1相关联。在各种生理生长条件下，可以培育出活性较高的P23基因替换突变体，并确认为零突变体，而不会对其活性产生不良影响。零突变体还表现出近乎野生型的传染性，反对P23在实验室环境中发挥决定性作用。然而，P23缺失突变体对HSP90抑制剂格尔达那霉素和自由基表现出显著的超敏反应。P23似乎也影响前面描述的HSP90Leu(33)-Ile突变体的自由基抗性。因此，证实了杜诺瓦尼乳杆菌P23是HSP90相互作用的辅助伴侣。
In Leishmania donovani, the HSP90 chaperone complex plays an essential role in the control of the parasite's life cycle, general viability and infectivity. Several of the associated co-chaperones were also shown to be essential for viability and/or infectivity to mammalian cells. Here, we identify and describe the co-chaperone P23 and distinguish its function from that of the structurally related small heat shock protein HSP23. P23 is expressed constitutively and associates itself with members of the HSP90 complex, i.e. HSP90 and Sti1. Viable P23 gene replacement mutants could be raised and confirmed as null mutants without deleterious effects on viability under a variety of physiological growth conditions. The null mutant also displays near-wild-type infectivity, arguing against a decisive role played by P23 in laboratory settings. However, the P23 null mutant displays a marked hypersensitivity against HSP90 inhibitors geldanamycin and radicicol. P23 also appears to affect the radicicol resistance of a HSP90 Leu(33)-Ile mutant described previously. Therefore, the annotation of L. donovani P23 as HSP90-interacting co-chaperone is confirmed.