Structural polymorphism in the N-terminal oligomerization domain of NPM1

Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4466-71. doi: 10.1073/pnas.1321007111. Epub 2014 Mar 10.


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.

Keywords: NMR; X-ray crystallography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Biopolymers / chemistry*
  • Biopolymers / metabolism
  • Chromatography, Gel
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Native Polyacrylamide Gel Electrophoresis
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Phosphorylation
  • Protein Binding
  • Protein Conformation


  • Biopolymers
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin

Associated data

  • PDB/4N8M