Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors /

Claus Schmitz; Mariusz Madej; Zuzanna Nowakowska; Anna Cuppari; Anna Jacula; Miroslaw Ksiazek; Katarzyna Mikruta; Jerzy Wisniewski; Natalia Pudelko-Malik; Anshu Saran; Natalie Zeytuni; Piotr Mlynarz; Richard J Lamont; Isabel Usón; Virginijus Šikšnys; Jan Potempa; Maria Solà

doi:10.1093/nar/gkac1103

Title	Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors /
Authors	Schmitz, Claus ; Madej, Mariusz ; Nowakowska, Zuzanna ; Cuppari, Anna ; Jacula, Anna ; Ksiazek, Miroslaw ; Mikruta, Katarzyna ; Wisniewski, Jerzy ; Pudelko-Malik, Natalia ; Saran, Anshu ; Zeytuni, Natalie ; Mlynarz, Piotr ; Lamont, Richard J ; Usón, Isabel ; Šikšnys, Virginijus ; Potempa, Jan ; Solà, Maria
DOI	10.1093/nar/gkac1103
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Is Part of	Nucleic acids research.. Oxford : Oxford University Press. 2022, vol. 50, no. 21, p. 12558-12577.. ISSN 0305-1048. eISSN 1362-4962
Keywords [eng]	PorX ; PglZ ; virulence factor
Abstract [eng]	The PglZ family of proteins belongs to the alkaline phosphatase superfamily, which consists of metallohydrolases with limited sequence identity but similar metal-coordination architectures in otherwise divergent active sites. Proteins with a well-defined PglZ domain are ubiquitous among prokaryotes as essential components of BREX phage defence systems and two-component systems (TCSs). Whereas other members of the alkaline phosphatase superfamily are well characterized, the activity, structure and biological function of PglZ family proteins remain unclear. We therefore investigated the structure and function of PorX, an orphan response regulator of the Porphyromonas gingivalis TCS containing a putative PglZ effector domain. The crystal structure of PorX revealed a canonical receiver domain, a helical bundle, and an unprecedented PglZ domain, similar to the general organization of the phylogenetically related BREX-PglZ proteins. The PglZ domain of PorX features an active site cleft suitable for large substrates. An extensive search for substrates revealed that PorX is a phosphodiesterase that acts on cyclic and linear oligonucleotides, including signalling molecules such as cyclic oligoadenylates. These results, combined with mutagenesis, biophysical and enzymatic analysis, suggest that PorX coordinates oligonucleotide signalling pathways and indirectly regulates gene expression to control the secretion of virulence factors.
Published	Oxford : Oxford University Press
Type	Journal article
Language	English
Publication date	2022
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„Response regulator PorX coordinates oligonucleotide signalling and gene expression to control the secretion of virulence factors /“