title: Phage dUTPases control transfer of virulence genes by a proto-oncogenic G protein-like mechanism.
abstract: dUTPases (Duts) have emerged as promising regulatory molecules controlling relevant cellular processes. However, the mechanism underlying this regulatory function remains enigmatic. Using staphylococcal pathogenicity island (SaPI) repression as a model, we report here that phage Duts induce the transfer of SaPI-encoded virulence factors by switching between active (dUTP-bound) and inactive (apo state) conformations, a conversion catalyzed by their intrinsic dUTPase activity. Crystallographic and mutagenic analyses demonstrate that binding to dUTP reorders the C-terminal motif V of the phage-encoded Duts, rendering these proteins into the active conformation required for SaPI derepression. By contrast, the conversion to the apo state conformation by hydrolysis of the bound dUTP generates a protein that is unable to induce the SaPI cycle. Because none of the requirements involving Duts in SaPI transfer are exclusive to the phage-encoded proteins, we propose that Duts are widespread cellular regulators acting in a manner analogous to the eukaryotic G proteins.
authors: Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA), Segorbe, 12400 Castellón, Spain.
authors: María Ángeles
authors: MÁ
authors: Tormo-Más
authors: Jorge
authors: J
authors: Donderis
authors: María
authors: M
authors: García-Caballer
authors: Aaron
authors: A
authors: Alt
authors: Ignacio
authors: I
authors: Mir-Sanchis
authors: Alberto
authors: A
authors: Marina
authors: José R
authors: JR
authors: Penadés
mesh_terms: D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044404:Genomic Islands / Q000235:genetics*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D013379:Substrate Specificity; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D014764:Viral Proteins; D019204:GTP-Binding Proteins; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase