Hombach Antje, Ommen Gabi, Sattler Victoria, Clos Joachim
Bernhard Nocht Institute for Tropical Medicine, P.O. Box 30 41 20, 20324, Hamburg, Germany.
Cell Stress Chaperones. 2015 Jul;20(4):673-85. doi: 10.1007/s12192-015-0595-y. Epub 2015 May 7.
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 Leu33-Ile mutant described previously. Therefore, the annotation of L. donovani P23 as HSP90-interacting co-chaperone is confirmed.
在杜氏利什曼原虫中，热休克蛋白90（HSP90）伴侣复合体在控制寄生虫的生命周期、总体生存能力和感染性方面发挥着至关重要的作用。一些相关的共伴侣蛋白也被证明对其生存能力和/或对哺乳动物细胞的感染性至关重要。在此，我们鉴定并描述了共伴侣蛋白P23，并将其功能与结构相关的小热休克蛋白HSP23的功能区分开来。P23组成性表达，并与HSP90复合体的成员，即HSP90和Sti1相互作用。可以培育出有活力的P23基因替代突变体，并确认为无效突变体，在各种生理生长条件下对生存能力没有有害影响。该无效突变体也表现出接近野生型的感染性，这表明在实验室条件下P23没有起决定性作用。然而，P23无效突变体对HSP90抑制剂格尔德霉素和雷帕霉素表现出明显的超敏感性。P23似乎也影响先前描述的HSP90 Leu33 - Ile突变体对雷帕霉素的抗性。因此，杜氏利什曼原虫P23作为与HSP90相互作用的共伴侣蛋白的注释得到了证实。
