title: Structural polymorphism in the N-terminal oligomerization domain of NPM1.
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.
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Mitrea
authors.forename: Christy R
authors.initials: CR
authors.lastname: Grace
authors.forename: Marija
authors.initials: M
authors.lastname: Buljan
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Yun
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Pytel
authors.forename: John
authors.initials: J
authors.lastname: Satumba
authors.forename: Amanda
authors.initials: A
authors.lastname: Nourse
authors.forename: Cheon-Gil
authors.initials: CG
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Madan Babu
authors.forename: Stephen W
authors.initials: SW
authors.lastname: White
authors.forename: Richard W
authors.initials: RW
authors.lastname: Kriwacki
mesh_terms: D000595:Amino Acid Sequence; D001704:Biopolymers / Q000737:chemistry* / Q000378:metabolism; D002850:Chromatography, Gel; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D063347:Native Polyacrylamide Gel Electrophoresis; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D000090243:Nucleophosmin; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001704:Biopolymers; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: NMR; X-ray crystallography