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Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism

DOI: 10.1016/j.molcel.2012.12.013 DOI Help
PMID: 23333307 PMID Help

Authors: Maria angeles Tormo-mas (Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA)) , Jorge Donderis (Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC)) , Mari­a Garci­a-caballer (Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA); Universidad Cardenal Herrera-CEU) , Aaron Alt (Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC)) , Ignacio Mir-sanchis (Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA)) , Alberto Marina (Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC); Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)) , Jose Penades (Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC); Universidad Cardenal Herrera-CEU)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 49 (5) , PAGES 947 - 958

State: Published (Approved)
Published: March 2013
Diamond Proposal Number(s): 8035

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.

Journal Keywords: GTP-Binding; Genomic; Models; Molecular; Protein; Tertiary; Pyrophosphatases; Staphylococcus; Substrate; Viral; Virulence

Subject Areas: Biology and Bio-materials, Medicine, Chemistry


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: ESRF