Phage dUTPases control transfer of virulence genes by a proto-oncogenic G protein-like mechanism

Tormo-Más, M.A., Donderis, J., García-Caballer, M., Alt, A., Mir-Sanchis, I., Marina, A. and Penades, J.R. (2013) Phage dUTPases control transfer of virulence genes by a proto-oncogenic G protein-like mechanism. Molecular Cell, 49(5), pp. 947-958. (doi:10.1016/j.molcel.2012.12.013)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Penades, Professor Jose R
Authors: Tormo-Más, M.A., Donderis, J., García-Caballer, M., Alt, A., Mir-Sanchis, I., Marina, A., and Penades, J.R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular Cell
ISSN:1097-2765

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