Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism
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 tran...
| Autores principales: | , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
2017
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| Acceso en línea: | http://hdl.handle.net/20.500.11939/4295 |
| _version_ | 1855491728233988096 |
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| author | Tormo-Mas, María A. Donderis, Jorge Garcia-Caballer, Maria Alt, Aaron Mir, Ignacio Marina, Alberto Penadés, José R. |
| author_browse | Alt, Aaron Donderis, Jorge Garcia-Caballer, Maria Marina, Alberto Mir, Ignacio Penadés, José R. Tormo-Mas, María A. |
| author_facet | Tormo-Mas, María A. Donderis, Jorge Garcia-Caballer, Maria Alt, Aaron Mir, Ignacio Marina, Alberto Penadés, José R. |
| author_sort | Tormo-Mas, María A. |
| collection | ReDivia |
| description | 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. |
| format | Artículo |
| id | ReDivia4295 |
| institution | Instituto Valenciano de Investigaciones Agrarias (IVIA) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | ReDivia42952025-04-25T14:42:46Z Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism Tormo-Mas, María A. Donderis, Jorge Garcia-Caballer, Maria Alt, Aaron Mir, Ignacio Marina, Alberto Penadés, José R. 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. 2017-06-01T10:09:48Z 2017-06-01T10:09:48Z 2013 MAR 7 2013 article Angeles 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. 1097-2765 http://hdl.handle.net/20.500.11939/4295 10.1016/j.molcel.2012.12.013 en openAccess Impreso |
| spellingShingle | Tormo-Mas, María A. Donderis, Jorge Garcia-Caballer, Maria Alt, Aaron Mir, Ignacio Marina, Alberto Penadés, José R. Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title | Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title_full | Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title_fullStr | Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title_full_unstemmed | Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title_short | Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism |
| title_sort | phage dutpases control transfer of virulence genes by a proto oncogenic g protein like mechanism |
| url | http://hdl.handle.net/20.500.11939/4295 |
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