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

AuthorsTormo-Más, María Ángeles; Donderis, Jorge ; García-Caballer, María; Alt, Aaron; Mir-Sanchis, Ignacio; Marina, Alberto ; Penadés, José R.
KeywordsStaphylococcus aureus
Pathogenicity island
SaPI induction
Gene transfer
Moonlighting proteins
G protein
Issue Date17-Jan-2013
Cell Press
CitationMolecular Cell 49(5):947-58 (2013)
AbstractdUTPases (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.
Description12 páginas, 7 figuras, 1 tabla. Se incluye post-print y material suplementario en fichero.
Publisher version (URL)http://dx.doi.org/10.1016/j.molcel.2012.12.013
Appears in Collections:(IBV) Artículos
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