Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization

PLoS Pathogens

María Angeles Tormo-Mas¹  Janine Bowring²  José R. Penadés²  Jorge Donderis³  J. Rafael Ciges-Tomas³  Iltyar Mehmedov³  Elisa Maiques³  Christian Alite³  Alberto Marina³ 

[1] Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain;Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;Instituto de Biomedicina de Valencia (IBV-CSIC) and CIBER de Enfermedades Raras (CIBERER), Valencia, Spain

关键词: Bacteriophages;    Sequence motif analysis;    Staphylococcus aureus;    Sequence alignment;    Staphylococcus;    Dimers (Chemical physics);    Crystal structure;    Phylogenetic analysis;   

DOI  :  10.1371/journal.ppat.1006581

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The dUTPase (Dut) enzymes, encoded by almost all free-living organisms and some viruses, prevent the misincorporation of uracil into DNA. We previously proposed that trimeric Duts are regulatory proteins involved in different cellular processes; including the phage-mediated transfer of the Staphylococcus aureus pathogenicity island SaPIbov1. Recently, it has been shown that the structurally unrelated dimeric Dut encoded by phage ϕNM1 is similarly able to mobilize SaPIbov1, suggesting dimeric Duts could also be regulatory proteins. How this is accomplished remains unsolved. Here, using in vivo, biochemical and structural approaches, we provide insights into the signaling mechanism used by the dimeric Duts to induce the SaPIbov1 cycle. As reported for the trimeric Duts, dimeric Duts contain an extremely variable region, here named domain VI, which is involved in the regulatory capacity of these enzymes. Remarkably, our results also show that the dimeric Dut signaling mechanism is modulated by dUTP, as with the trimeric Duts. Overall, our results demonstrate that although unrelated both in sequence and structure, dimeric and trimeric Duts control SaPI transfer by analogous mechanisms, representing a fascinating example of convergent evolution. This conserved mode of action highlights the biological significance of Duts as regulatory molecules.

【 授权许可】

CC BY