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The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression

The transcriptional antisilencer VirB acts as a master regulator of virulence gene expression in the human pathogen Shigella flexneri. It binds DNA sequences (virS) upstream of VirB-dependent promoters and counteracts their silencing by the nucleoid-organizing protein H-NS. However, its precise mode...

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Main Authors: Jakob, Sara (Author) , Steinchen, Wieland (Author) , Hanßmann, Juri (Author) , Rosum, Julia (Author) , Langenfeld, Katja (Author) , Osorio Valeriano, Manuel (Author) , Steube, Niklas (Author) , Giammarinaro, Pietro Ivan (Author) , Hochberg, Georg K. A. (Author) , Glatter, Timo (Author) , Bange, Gert (Author) , Diepold, Andreas (Author) , Thanbichler, Martin Rudolf (Author)
Format: Article (Journal)
Language:English
Published: 05 January 2024
In: Nature Communications
Year: 2024, Volume: 15, Pages: 1-18
ISSN:2041-1723
DOI:10.1038/s41467-023-44509-z
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-023-44509-z
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-023-44509-z
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Author Notes:Sara Jakob, Wieland Steinchen, Juri Hanßmann, Julia Rosum, Katja Langenfeld, Manuel Osorio-Valeriano, Niklas Steube, Pietro I. Giammarinaro, Georg K.A. Hochberg, Timo Glatter, Gert Bange, Andreas Diepold & Martin Thanbichler
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Summary:The transcriptional antisilencer VirB acts as a master regulator of virulence gene expression in the human pathogen Shigella flexneri. It binds DNA sequences (virS) upstream of VirB-dependent promoters and counteracts their silencing by the nucleoid-organizing protein H-NS. However, its precise mode of action remains unclear. Notably, VirB is not a classical transcription factor but related to ParB-type DNA-partitioning proteins, which have recently been recognized as DNA-sliding clamps using CTP binding and hydrolysis to control their DNA entry gate. Here, we show that VirB binds CTP, embraces DNA in a clamp-like fashion upon its CTP-dependent loading at virS sites and slides laterally on DNA after clamp closure. Mutations that prevent CTP-binding block VirB loading in vitro and abolish the formation of VirB nucleoprotein complexes as well as virulence gene expression in vivo. Thus, VirB represents a CTP-dependent molecular switch that uses a loading-and-sliding mechanism to control transcription during bacterial pathogenesis.
Item Description:Gesehen am 14.03.2024
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-023-44509-z

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