A mutation in intracellular loop 4 affects the drug-efflux activity of the yeast multidrug resistance ABC transporter Pdr5p.
A mutation in intracellular loop 4 affects the drug-efflux activity of the yeast multidrug resistance ABC transporter Pdr5p.
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细胞内环 4 的突变影响酵母多药耐药性 ABC 转运蛋白 Pdr5p 的药物流出活性
DOI：
10.1371/journal.pone.0029520
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Guo X;Li J;Wang T;Liu Z;Chen X;Li Y;Gu Z;Mao X;Guan W;Li Y
多药耐药蛋白Pdr5p是酵母细胞质膜上的三磷酸腺苷结合盒(ABC)转运蛋白。它通过主动外排细胞内药物而产生多药耐药。然而，临床菌株YJM789的高度多态的Pdr5p失去了排除唑和环己胺的能力。为了研究氨基酸变化在这种功能变化中的作用，用同源的BY4741 PDR5片段分段替换构建了PDR5嵌合体。用氟康唑和放线菌酮抗性试验评价PDR5嵌合体的功能。分析了它们的表达、ATPase活性和对其他底物的外排效率。利用多条证据，我们证明了位于预测的短胞内环4的1352位丙氨酸到蛋氨酸的突变显著地导致了观察到的转运缺陷。损伤的程度可能与突变残基的大小有关。
Multidrug resistance protein Pdr5p is a yeast ATP-binding cassette (ABC) transporter in the plasma membrane. It confers multidrug resistance by active efflux of intracellular drugs. However, the highly polymorphic Pdr5p from clinical strain YJM789 loses its ability to expel azole and cyclohexmide. To investigate the role of amino acid changes in this functional change, PDR5 chimeras were constructed by segmental replacement of homologous BY4741 PDR5 fragments. Functions of PDR5 chimeras were evaluated by fluconazole and cycloheximide resistance assays. Their expression, ATPase activity, and efflux efficiency for other substrates were also analyzed. Using multiple lines of evidence, we show that an alanine-to-methionine mutation at position 1352 located in the predicted short intracellular loop 4 significantly contributes to the observed transport deficiency. The degree of impairment is likely correlated to the size of the mutant residue.
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影响因子：
14.8
作者：
Gietz, R. Daniel;Schiestl, Robert H.
通讯作者：
Schiestl, Robert H.
影响因子：
3.6
作者：
Egner, R;Bauer, BE;Kuchler, K
通讯作者：
Kuchler, K
影响因子：
4.8
作者：
Kolaczkowski, M;vanderRest, M;Goffeau, A
通讯作者：
Goffeau, A
DOI：
10.1073/pnas.0800191105
发表时间：
2008-04-01
影响因子：
11.1
作者：
Ernst, Robert;Kueppers, Petra;Schmitt, Lutz
通讯作者：
Schmitt, Lutz
影响因子：
3
作者：
Rutledge, Robert M.;Esser, Lothar;Ma, Jichun;Xia, Di
通讯作者：
Xia, Di