Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein.
The retinoblastoma susceptibility protein RB1 is a key regulator of cell proliferation and fate. RB1 operates through nucleating the formation of multi-component protein complexes involved in the regulation of gene transcription, chromatin structure and protein stability. Phosphorylation of RB1 by c...
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| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0058463&type=printable |
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| author | Ekaterina P Lamber Fabienne Beuron Edward P Morris Dmitri I Svergun Sibylle Mittnacht |
| author_facet | Ekaterina P Lamber Fabienne Beuron Edward P Morris Dmitri I Svergun Sibylle Mittnacht |
| author_sort | Ekaterina P Lamber |
| collection | DOAJ |
| description | The retinoblastoma susceptibility protein RB1 is a key regulator of cell proliferation and fate. RB1 operates through nucleating the formation of multi-component protein complexes involved in the regulation of gene transcription, chromatin structure and protein stability. Phosphorylation of RB1 by cyclin-dependent kinases leads to conformational alterations and inactivates the capability of RB1 to bind partner protein. Using small angle X-ray scattering in combination with single particle analysis of transmission electron microscope images of negative-stained material we present the first three-dimensional reconstruction of non-phosphorylated RB1 revealing an extended architecture and deduce the domain arrangement within the molecule. Phosphorylation results in an overt alteration of the molecular shape and dimensions, consistent with the transition to a compact globular architecture. The work presented provides what is to our knowledge the first description of the relative domain arrangement in active RB1 and predicts the molecular movement that leads to RB1 inactivation following protein phosphorylation. |
| format | Article |
| id | doaj-art-2aab6e6b2e564bac8a760624e0f3f00a |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2aab6e6b2e564bac8a760624e0f3f00a2025-08-20T03:25:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5846310.1371/journal.pone.0058463Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein.Ekaterina P LamberFabienne BeuronEdward P MorrisDmitri I SvergunSibylle MittnachtThe retinoblastoma susceptibility protein RB1 is a key regulator of cell proliferation and fate. RB1 operates through nucleating the formation of multi-component protein complexes involved in the regulation of gene transcription, chromatin structure and protein stability. Phosphorylation of RB1 by cyclin-dependent kinases leads to conformational alterations and inactivates the capability of RB1 to bind partner protein. Using small angle X-ray scattering in combination with single particle analysis of transmission electron microscope images of negative-stained material we present the first three-dimensional reconstruction of non-phosphorylated RB1 revealing an extended architecture and deduce the domain arrangement within the molecule. Phosphorylation results in an overt alteration of the molecular shape and dimensions, consistent with the transition to a compact globular architecture. The work presented provides what is to our knowledge the first description of the relative domain arrangement in active RB1 and predicts the molecular movement that leads to RB1 inactivation following protein phosphorylation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0058463&type=printable |
| spellingShingle | Ekaterina P Lamber Fabienne Beuron Edward P Morris Dmitri I Svergun Sibylle Mittnacht Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. PLoS ONE |
| title | Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. |
| title_full | Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. |
| title_fullStr | Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. |
| title_full_unstemmed | Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. |
| title_short | Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. |
| title_sort | structural insights into the mechanism of phosphoregulation of the retinoblastoma protein |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0058463&type=printable |
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