| First Author | Mitrea DM | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 12 | Pages | 4466-71 |
| PubMed ID | 24616519 | Mgi Jnum | J:207374 |
| Mgi Id | MGI:5556305 | Doi | 10.1073/pnas.1321007111 |
| Citation | Mitrea DM, et al. (2014) Structural polymorphism in the N-terminal oligomerization domain of NPM1. Proc Natl Acad Sci U S A 111(12):4466-71 |
| abstractText | 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. |
