4N8M

Structural polymorphism in the N-terminal oligomerization domain of NPM1

Summary for 4N8M

• Entry DOI: 10.2210/pdb4n8m/pdb
• Descriptor: Nucleophosmin, COBALT (II) ION (3 entities in total)
• Functional Keywords: histone chaperone, nucleolar protein, phosphoprotein, structural polymorphism, pentamer, ribosome biogenesis, regulated unfolding, chaperone
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 5
• Total formula weight: 73371.07

Authors

Mitrea, D.,Royappa, G.,Buljan, M.,Yun, M.,Pytel, N.,Satumba, J.,Nourse, A.,Park, C.,Babu, M.M.,White, S.W.,Kriwacki, R.W. (deposition date: 2013-10-17, release date: 2014-03-12, Last modification date: 2023-09-20)

Primary citation

Mitrea, D.M.,Grace, C.R.,Buljan, M.,Yun, M.K.,Pytel, N.J.,Satumba, J.,Nourse, A.,Park, C.G.,Madan Babu, M.,White, S.W.,Kriwacki, R.W.
Structural polymorphism in the N-terminal oligomerization domain of NPM1.
Proc.Natl.Acad.Sci.USA, 111:4466-4471, 2014

PubMed Abstract: 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.

PubMed: 24616519
DOI: 10.1073/pnas.1321007111

Experimental method

X-RAY DIFFRACTION (1.802 Å)