3ZF4

Phage dUTPases control transfer of virulence genes by a proto- oncogenic G protein-like mechanism. (Staphylococcus bacteriophage 80alpha dUTPase Y81A mutant with dUpNHpp).

Summary for 3ZF4

• Entry DOI: 10.2210/pdb3zf4/pdb
• Related: 3ZEZ 3ZF0 3ZF1 3ZF2 3ZF3 3ZF5 3ZF6
• Descriptor: DUTPASE, 2'-DEOXYURIDINE 5'-ALPHA,BETA-IMIDO-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, pathogenicity island, sapi induction, gene transfer, moonlighting proteins, g-protein, p-loop
• Biological source: STAPHYLOCOCCUS PHAGE 80ALPHA
• Total number of polymer chains: 1
• Total formula weight: 23184.38

Authors

Tormo-Mas, M.A.,Donderis, J.,Garcia-Caballer, M.,Alt, A.,Mir-Sanchis, I.,Marina, A.,Penades, J.R. (deposition date: 2012-12-10, release date: 2013-01-30, Last modification date: 2023-12-20)

Primary citation

Tormo-Mas, M.A.,Donderis, J.,Garcia-Caballer, M.,Alt, A.,Mir-Sanchis, I.,Marina, A.,Penades, J.R.
Phage Dutpases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-Like Mechanism.
Mol.Cell, 49:947-, 2013

PubMed 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.

PubMed: 23333307
DOI: 10.1016/J.MOLCEL.2012.12.013

Experimental method

X-RAY DIFFRACTION (3.1 Å)