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

Jakob, S., Steinchen, W., Hanßmann, J., Rosum, J., Langenfeld, K., Osorio-Valeriano, M., et al. (2024). The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression. Nature Communications, 15(1): 318. doi:10.1038/s41467-023-44509-z.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000E-2030-7 Version Permalink: https://hdl.handle.net/21.11116/0000-000F-2F09-4
Genre: Journal Article

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https://doi.org/10.1038/s41467-023-44509-z (Publisher version)
Description:
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OA-Status:
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 Creators:
Jakob, Sara1, Author
Steinchen, Wieland1, Author
Hanßmann, Juri1, 2, Author           
Rosum, Julia1, Author
Langenfeld, Katja3, Author           
Osorio-Valeriano, Manuel1, Author
Steube, Niklas4, Author           
Giammarinaro, Pietro I.1, Author
Hochberg, Georg K. A.4, Author                 
Glatter, Timo5, Author                 
Bange, Gert1, 6, Author                 
Diepold, Andreas3, Author                 
Thanbichler, Martin1, 2, Author                 
Affiliations:
1external, ou_persistent22              
2Max Planck Fellow Bacterial Cell Biology, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3266301              
3Research Group Bacterial Secretion Systems, Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3266306              
4Max Planck Research Group Evolutionary Biochemistry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3266300              
5Core Facility Mass Spectrometry and Proteomics, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3266266              
6Max Planck Fellow Molecular Physiology of Microbes, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3321791              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2023-12-112024
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: URI: https://doi.org/10.1038/s41467-023-44509-z
Other: Jakob2024
DOI: 10.1038/s41467-023-44509-z
 Degree: -

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Project name : -
Grant ID : -
Funding program : -
Funding organization : Max Planck Society
Project name : C-SWITCH
Grant ID : 101097986
Funding program : -
Funding organization : European Research Council
Project name : TRR 174
Grant ID : 269423233
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : DFG Core Facility for Interactions, Dynamics and Assembly of Biomolecular Structures
Grant ID : 324652314
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Projekt DEAL

Source 1

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 15 (1) Sequence Number: 318 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723