期刊
MOLECULAR CELL
卷 81, 期 1, 页码 139-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2020.10.035
关键词
-
资金
- National Institutes of Health [R35GM130290, R21AI146641, AI081693, AI145954, F31AI150138, HD055148-08, R01GM124149, P30GM124169, U24GM129547]
- University of California Office of the President, Multicampus Research Programs and Initiatives grant [MR-15-328599]
- US Department of Energy [DE-AC02-05CH11231]
- Office of Biological and Environmental Research
- National Science Foundation, National Nanotechnology Coordinated Infrastructure (NNCI) [ECCS-2025064]
This study reveals a unique mechanism for Ft pathogenesis involving a virulence-specialized RNAP that employs two (MglA-SspA)-based strategies to activate virulence genes.
The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with the sigma(70)-associated RNAP holoenzyme (RNAP sigma(70)), forming a virulence-specialized polymerase. These factors activate Francisella pathogenicity island (FPI) gene expression, which is required for virulence, but the mechanism is unknown. Here we report FtRNAP sigma(70)-promoter-DNA, FtRNAP sigma(70)-(MglA-SspA)-promoter DNA, and FtRNAP sigma(70)-(MglA-SspA)-ppGpp-PigR-promoter DNA cryo-EM structures. Structural and genetic analyses show MglA-SspA facilitates sigma(70) binding to DNA to regulate virulence and virulence-enhancing genes. Our Escherichia coli RNAP sigma(70)-homodimeric EcSspA structure suggests this is a general SspA-transcription regulation mechanism. Strikingly, our FtRNAP sigma(70)-(MglA-SspA)-ppGpp-PigR-DNA structure reveals ppGpp binding to MglA-SspA tethers PigR to promoters. PigR in turn recruits FtRNAP alpha CTDs to DNA UP elements. Thus, these studies unveil a unique mechanism for Ft pathogenesis involving a virulence-specialized RNAP that employs two (MglA-SspA)-based strategies to activate virulence genes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据