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Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein.

Lamber, EP; Beuron, F; Morris, EP; Svergun, DI; Mittnacht, S; (2013) Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein. PLoS One , 8 (3) , Article e58463. 10.1371/journal.pone.0058463. Green open access

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Abstract

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.

Type: Article
Title: Structural insights into the mechanism of phosphoregulation of the retinoblastoma protein.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0058463
Publisher version: http://dx.doi.org/10.1371/journal.pone.0058463
Language: English
Additional information: © 2013 Lamber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3597711
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1389748
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