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Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization

DOI: 10.1371/journal.ppat.1006581 DOI Help

Authors: Jorge Donderis (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER)) , Janine Bowring (University of Glasgow) , Elisa Maiques (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER)) , J. Rafael Ciges-tomas (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER)) , Christian Alite (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER)) , Iltyar Mehmedov (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER)) , María Angeles Tormo-mas (Universidad CEU Cardenal Herrera) , José R. Penadés (University of Glasgow) , Alberto Marina (Instituto de Biomedicina de Valencia (IBV-CSIC); CIBER de Enfermedades Raras (CIBERER))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 13

State: Published (Approved)
Published: September 2017
Diamond Proposal Number(s): 14739

Open Access Open Access

Abstract: 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.

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

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography