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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 {angstrom} 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:
; ; ;
Publication Date:
Research Org.:
BROOKHAVEN NATIONAL LABORATORY (BNL)
Sponsoring Org.:
USDOE SC OFFICE OF SCIENCE (SC)
OSTI Identifier:
1041951
Report Number(s):
BNL-97629-2012-JA
Journal ID: ISSN 0006-2960; BICHAW; TRN: US201212%%362
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry (Eaton); Journal Volume: 50; Journal Issue: 37
Country of Publication:
United States
Language:
English
Subject:
08 HYDROGEN; CRYSTAL STRUCTURE; DIMERS; EMBRYOS; ENERGY TRANSFER; FLUORESCENCE; HISTONES; HYDROGEN; MUTATIONS; OOCYTES; RESIDUES; RESOLUTION; RESONANCE

Citation Formats

O Platonova, I Akey, J Head, and C Akey. Crystal Structure and Function of Human Nucleoplasmin (Npm2): A Histone Chaperone in Oocytes and Embryos. United States: N. p., 2011. Web. doi:10.1021/bi2006652.
O Platonova, I Akey, J Head, & C Akey. Crystal Structure and Function of Human Nucleoplasmin (Npm2): A Histone Chaperone in Oocytes and Embryos. United States. doi:10.1021/bi2006652.
O Platonova, I Akey, J Head, and C Akey. Sat . "Crystal Structure and Function of Human Nucleoplasmin (Npm2): A Histone Chaperone in Oocytes and Embryos". United States. doi:10.1021/bi2006652.
@article{osti_1041951,
title = {Crystal Structure and Function of Human Nucleoplasmin (Npm2): A Histone Chaperone in Oocytes and Embryos},
author = {O Platonova and I Akey and J Head and C Akey},
abstractNote = {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 {angstrom} 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.},
doi = {10.1021/bi2006652},
journal = {Biochemistry (Eaton)},
number = 37,
volume = 50,
place = {United States},
year = {Sat Dec 31 00:00:00 EST 2011},
month = {Sat Dec 31 00:00:00 EST 2011}
}