Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 12, Pages 4466-4471Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1321007111
Keywords
NMR; X-ray crystallography
Categories
Funding
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
- National Institutes of Health [5RO1-CAO82491, 5R01-GM083159, P30CA21765]
- MRC [MC_U105185859]
- HFSP [RGY0073/2010]
- ALSAC
- MRC [MC_U105185859] Funding Source: UKRI
- Medical Research Council [MC_U105185859] Funding Source: researchfish
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Nucleophosmin (NPM1) is a multifunctional phospho-protein with critical roles in ribosome biogenesis, tumor suppression, and nucleolar stress response. Here we show that the N-terminal oligomerization domain of NPM1 (Npm-N) exhibits structural polymorphism by populating conformational states ranging from a highly ordered, folded pentamer to a highly disordered monomer. The monomer-pentamer equilibrium is modulated by posttranslational modification and protein binding. Phosphorylation drives the equilibrium in favor of monomeric forms, and this effect can be reversed by Npm-N binding to its interaction partners. We have identified a short, arginine-rich linear motif in NPM1 binding partners that mediates Npm-N oligomerization. We propose that the diverse functional repertoire associated with NPM1 is controlled through a regulated unfolding mechanism signaled through posttranslational modifications and intermolecular interactions.
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