HDX and Native Mass Spectrometry Reveals the Different Structural Basis for Interaction of the Staphylococcal Pathogenicity Island Repressor Stl with Dimeric and Trimeric Phage dUTPases

Kinga Nyíri, Matthew J. Harris, Judit Matejka, Olivér Ozohanics, Károly Vékey, Antoni J. Borysik, Beáta G. Vértessy

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The dUTPase enzyme family plays an essential role in maintaining the genome integrity and are represented by two distinct classes of proteins; the β-pleated homotrimeric and the all-α homodimeric dUTPases. Representatives of both trimeric and dimeric dUTPases are encoded by Staphylococcus aureus phage genomes and have been shown to interact with the Stl repressor protein of S. aureus pathogenicity island SaPIbov1. In the present work we set out to characterize the interactions between these proteins based on a range of biochemical and biophysical methods and shed light on the binding mechanism of the dimeric φNM1 phage dUTPase and Stl. Using hydrogen deuterium exchange mass spectrometry, we also characterize the protein regions involved in the dUTPase:Stl interactions. Based on these results we provide reasonable explanation for the enzyme inhibitory effect of Stl observed in both types of complexes. Our experiments reveal that Stl employs different peptide segments and stoichiometry for the two different phage dUTPases which allows us to propose a functional plasticity of Stl. The malleable character of Stl serves as a basis for the inhibition of both dimeric and trimeric dUTPases.

Original languageEnglish
Article number488
JournalBiomolecules
Volume9
Issue number9
DOIs
Publication statusPublished - 14 Sept 2019

Keywords

  • DUTPase
  • Inhibition
  • Interaction surface
  • Stl staphylococcal repressor

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