Nucleoplasmin: A Versatile Histone Chaperone

Abstract

Cells have evolved an ingenious way to tightly pack the genetic information in a nucleoprotein complex called chromatin. The functional unit of chromatin is the nucleosome, which is made of DNA wrapped around histones. Dynamic modulation of nucleosome structure by regulating the association/dissociation of histones to/from DNA is essential for DNA replication, repair and transcription. In vivo, a group of histone chaperones facilitate and regulate nucleosome assembly. Recent structural, biophysical and biochemical studies have begun to shed light on the molecular mechanisms whereby histone chaperones promote chromatin assembly, disassembly and histone exchange. This review focuses on the structure and function of Nucleoplasmin (NP), a key component of the amphibian chromatin remodelling machinery during fertilisation and early embryonic development.

Key Concepts

  • Histone chaperones are key components of the machinery that regulates chromatin dynamics.
  • The function of histone chaperones is based on their interaction with histone surfaces involved in binding to DNA and other histones.
  • Histone chaperones can be classified into two main groups, specific and generic chaperones, according to their ability to bind only a particular histone or all kind of linker and core histones with similar affinity, respectively.
  • Nucleoplasmin is a generic histone chaperone able to interact with both linker and core histones.
  • Nucleoplasmin uses the same protein region, the intrinsically disordered, acidic distal face to interact with all histones, favouring competition for NP binding and thus histone exchange.
  • The oligomeric structure of NP builds a large histone‐binding region that allows the chaperone to bind different association states of histones, including the octamer.

Keywords: nucleoplasmin; histone chaperone; chromatin; nucleosome; histone; post‐translational modification; intrinsically disordered protein

Figure 1. Structure of different histone chaperone/histone complexes. Ribbon representations of YL1/H2A.Z‐H2B ‐PDB 5CHL‐ (a); HJURP/CENP‐A‐H4 ‐PDB 3R45‐ (b); CIA‐1/H3.1‐H4 ‐PDB 2IO5‐ (c) and Spt2/H3.2‐H4 ‐PDB 5BS7‐ (d) complexes. In each structure, the histone chaperone is shown in purple and histones H2A, H2B, H3 and H4 in yellow, blue, green and red, respectively. Histone regions that undergo a conformational rearrangement upon chaperone binding and impair histone–histone interactions are shown in orange.
Figure 2. Nucleoplasmin structure. (a) Schematic representation of the domain architecture of NP. The chaperone domains, acidic patches, the nuclear localisation signal and post‐translational modifications are located within the protein primary structure. (b) Ribbon representation of the structure of the core domain of one NP monomer. The acidic tract A1 is highlighted in green and the protein faces are labelled ‐PDB 1K5J‐. (c) Crystal structure of pentameric NP. The structure corresponds to the pentameric core domain ‐PDB 1K5J‐ (d) Side view of the 3D‐EM (electron microscopy) reconstruction of native eNP. The crystal structure of the core domain is docked into the mass of the full‐length reconstructed particle ‐EMD 1778‐.
Figure 3. Models for the interaction of NP with core histones. NP pentamer shows a cup‐like structure with the intrinsically disordered C‐terminal domains located in the distal protein face (a monomer in the pentameric structure is highlighted in dark). Core histones bind to the distal face forming different complexes. One H2A‐H2B dimer (red) interacts with the protein arm of one NP protomer that protrudes from the core, following the chaperone fivefold symmetry. In stark contrast, H3‐H4 tetramers (green), either alone or as part of the histone octamer, are stabilised within a cage‐like structure that follows the symmetry of the histone ligand. These binding models are based on EM studies of the different NP/core histones complexes. The location of the NP pentamers in the chaperone complexes with H3‐H4 tetramers and the histone octamer remains to be accurately determined and is suggested here considering the possible symmetry of the basic ligands.
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Franco, Aitor, Fernández‐Rivero, Noelia, Prado, Adelina, and Muga, Arturo(Jan 2017) Nucleoplasmin: A Versatile Histone Chaperone. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027010]