Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism
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AuthorTormo-Mas, María A.; Donderis, Jorge; Garcia-Caballer, Maria; Alt, Aaron; Mir, Ignacio; Marina, Alberto; Penadés, José R.
Cita bibliográficaAngeles Tormo-Mas, M., Donderis, J., Garcia-Caballer, M., Alt, Aaron, Mir-Sanchis, I., Marina, A., Penades, J.R. (2013). Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism. Molecular cell, 49(5), 947-958.
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.