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：2016
卷号：113
期号：51
页码：14733-14738
DOI：10.1073/pnas.1614028114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceInfection by the human bacterial pathogen Listeria monocytogenes is controlled mainly by the transcriptional activator PrfA, a member of the Crp/Fnr family. Here we report the crystal structures of PrfA in complex with glutathione (GSH) and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. The structures provide detailed information and insight into how GSH interacts with PrfA and thus induces the correct fold of the HTH motif promoting PrfA DNA binding. Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfAWT in complex only with DNA confirms that PrfAWT can adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.
