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

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-44509-z
Popis: 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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