文章基本信息

标题：Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR
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作者：Koh Takeuchi ; Koh Takeuchi ; Misaki Imai 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：40
页码：19963-19972
DOI：10.1073/pnas.1906129116
出版社：The National Academy of Sciences of the United States of America
摘要：QacR, a multidrug-binding transcriptional repressor in pathogenic bacteria Staphylococcus aureus , modulates the transcriptional level of the multidrug transporter gene, qacA , in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the repressive and inducive conformations in QacR defines the induction level of the transporter gene. In addition, the unligated QacR is already partly populated in the inducive conformation, allowing the basal expression of the transporter. We also showed that, in the known constitutively active QacR mutants, the equilibrium is shifted more toward the inducive conformation, even in the unligated state. These results highlight the unexpected structural mechanism, connecting the promiscuous multidrug binding to the variable transcriptional regulation of QacR, which provide clues to dysfunctioning of the multidrug resistance systems..
关键词：multidrug resistance ; transcription factor ; structure ; dynamics ; NMR