title: Crystal structure and function of human nucleoplasmin (npm2): a histone chaperone in oocytes and embryos.
abstract: Human Npm2 is an ortholog of Xenopus nucleoplasmin (Np), a chaperone that binds histones. We have determined the crystal structure of a truncated Npm2-core at 1.9 Å resolution and show that the N-terminal domains of Npm2 and Np form similar pentamers. This allowed us to model an Npm2 decamer which may be formed by hydrogen bonds between quasi-conserved residues in the interface between two pentamers. Interestingly, the Npm2 pentamer lacks a prototypical A1-acidic tract in each of its subunits. This feature may be responsible for the inability of Npm2-core to bind histones. However, Npm2 with a large acidic tract in its C-terminal tail (Npm2-A2) is able to bind histones and form large complexes. Fluorescence resonance energy transfer experiments and biochemical analysis of loop mutations support the premise that nucleoplasmins form decamers when they bind H2A-H2B dimers and H3-H4 tetramers simultaneously. In the absence of histone tetramers, these chaperones bind H2A-H2B dimers with a single pentamer forming the central hub. When taken together, our data provide insights into the mechanism of histone binding by nucleoplasmins.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany St., Boston, Massachusetts 02118-2526, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Platonova
authors.forename: Ildikó V
authors.initials: IV
authors.lastname: Akey
authors.forename: James F
authors.initials: JF
authors.lastname: Head
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Akey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods; D056488:Histone Chaperones / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D056489:Nucleoplasmins / Q000737:chemistry* / Q000502:physiology*; D009865:Oocytes / Q000737:chemistry* / Q000502:physiology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D056488:Histone Chaperones; C533550:NPM2 protein, human; D056489:Nucleoplasmins