Critical role of the proton-dependent oligopeptide transporter (POT) in the cellular uptake of the peptidyl nucleoside antibiotic, blasticidin S

Critical role of the proton-dependent oligopeptide transporter (POT) in the cellular uptake of the peptidyl nucleoside antibiotic, blasticidin S
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DOI:
10.1016/j.bbamcr.2016.11.030
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发表时间:
2017-02-01
影响因子:
5.1
通讯作者:
Abe, Fumiyoshi
Abe, Fumiyoshi
中科院分区:
生物学2区
文献类型:
--
作者:
Kitamura, Kenji;Kinsui, Eldaa Zefany Banami;Abe, Fumiyoshi

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BlaS干扰真核生物和原核生物的细胞生长。其作为蛋白质合成抑制剂的作用方式已被广泛研究。然而,BlaS转运到靶细胞的机制尚不清楚。在这里,我们发现Ptr2是质子依赖性寡肽转运体(POT)家族的成员,负责酵母裂糖酵母(Schizosaccharomyces pombe)和酿酒酵母(Saccharomyces cerevisiae)对BlaS的摄取。值得注意的是,一些在二肽摄取方面功能失调的Ptr2突变体仍然能够运输BlaS。小鼠来源的寡肽转运体PepT1赋予酿酒葡萄球菌ptr2 δ突变体BlaS敏感性。此外,细菌POT家族蛋白也增强了大肠杆菌对BlaS的敏感性。从细菌到哺乳动物,POT家族寡肽转运体在BlaS摄取中的作用是保守的。(C) 2016 Elsevier B.V.版权所有
Blasticidin S (BlaS) interferes in the cell growth of both eukaryotes and prokaryotes. Its mode of action as a protein synthesis inhibitor has been investigated extensively. However, the mechanism of BlaS transport into the target cells is not understood well. Here, we show that Ptr2, a member of the proton-dependent oligopeptide transporter (POT) family, is responsible for the uptake of BlaS in yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Notably, some mutants of Ptr2 that are dysfunctional in dipeptide uptake were still competent to transport BlaS. Mouse-derived oligopeptide transporter PepT1 conferred BlaS sensitivity in the S. cerevisiae ptr2 Delta mutant. Furthermore, bacterial POT family proteins also potentiated the BlaS sensitivity of E. coli. The role of the POT family oligopeptide transporters in the uptake of BlaS is conserved across species from bacteria to mammals. (C) 2016 Elsevier B.V. All rights reserved.