Structure-function relationship of H2A-H2B specific plant histone chaperones

Abstract

Studies on chromatin structure and function have gained a revived popularity. Histone chaperones are significant players in chromatin organization. They play a significant role in vital nuclear functions like transcription, DNA replication, DNA repair, DNA recombination, and epigenetic regulation, primarily by aiding processes such as histone shuttling and nucleosome assembly/disassembly. Like the other eukaryotes, plants also have a highly orchestrated and dynamic chromatin organization. Plants seem to have more isoforms within the same family of histone chaperones, as compared with other organisms. As some of these are specific to plants, they must have evolved to perform functions unique to plants. However, it appears that only little effort has gone into understanding the structural features of plant histone chaperones and their structure-function relationships. Studies on plant histone chaperones are essential for understanding their role in plant chromatin organization and how plants respond during stress conditions. This review is on the structural and functional aspects of plant histone chaperone families, specifically those which bind to H2A-H2B, viz nucleosome assembly protein (NAP), nucleoplasmin (NPM), and facilitates chromatin transcription (FACT). Here, we also present comparative analyses of these plant histone chaperones with available histone chaperone structures. The review hopes to incite interest among researchers to pursue further research in the area of plant chromatin and the associated histone chaperones.

Keywords: FACT; H2A-H2B; Histone chaperones; NAP1; NRP1; Nucleoplasmin.

Fig. 1

Domain organization, sequence alignment, and structure alignments of ScNAP1 and AtNAP1. a The figure shows the similarities and differences in the domain organization of S. cerevisiae and A. thaliana NAP1 proteins. The N-terminal disordered tail (NT), the dimerization domain (DD), the disordered C-terminal tail with Asp/Glu residues (CT), the nuclear export sequence (NES), and the nuclear localization sequence (NLS) are labeled. AtNAP1 has four different isoforms (not shown in this figure), with a similar domain organization, but differing in length, ranging from 317 to 379 residues. b Sequence alignment of AtNAP1;1, OsNAP1;1, and ScNAP1. Highlighted in yellow are the residues conserved in all three species; highlighted in cyan are residues conserved in at least two species. For the ScNAP1 sequence, underlined are the residues forming α-helices, and shown in red are the residues forming β-sheets. ClustalW multiple sequence alignment tool aided the alignment. c Structure alignment of modeled AtNAP1 (blue) with ScNAP1 (orange). The r.m.s.d deviation for AtNAP1 structure superimposed with ScNAP1 is 0.57 for 171 Cα atoms. The zoomed boxes show the offsets in the structure. d Surface charge distribution of AtNAP1 monomer model. Phyre2 server was used for the homology modeling

Fig. 2

Structure of NAP family proteins. a The structure superposition of ScNAP1 (PDB id, 2AYU) with AtNRP1 (PDB id, 5DAY). The structures align with an r.m.s.d. of 2.63 Å. AtNRP1 is in blue and ScNAP1 in orange. The dotted lines represent the flexible loop regions missing in the crystal structures. b The structure superposition of AtNRP1 (PDB id, 5DAY) and AtNRP2 (PDB id, 6JQV) with human SET/TAF-Iβ (PDB id, 2E50). The structures align with an r.m.s.d. of 2.37 Å. AtNRP1 is in blue, AtNRP2 in yellow, and SET/TAF-Iβ in cyan. Most of the secondary structural features align well in the three structures. The dotted lines represent the flexible loop regions missing in the crystal structures. c The structure of ScNAP1 in complex with histone H2A-H2B (PDB id, 5G2E). The dimeric structure of ScNAP1 reveals the mode of interaction with H2A-H2B. d A zoomed view of the interaction between ScNAP1 and the histones. Histone H2A is in violet, and H2B is in yellow. The residues forming the histone-binding region 1 (HBR1) of ScNAP1 are represented as blue sticks (D201, D205, and E310). The two significant residues of histone-binding region 2 (HBR2) are shown in green (E332 and E336). The L1 loop of H2A, which packs the HBR1 of ScNAP1, is also labeled.

Fig. 3

Domain organization and structure of nucleoplasmins. a The domain organization of the three classes of nucleoplasmins. The domains are labeled. The N-terminal core domain forms a pentamer in all nucleoplasmins. b, c The pentameric structure of the N-terminal domain of X. laevis nucleoplasmin (PDB id, 1K5J) in two different orientations. The five-fold axis is also shown in c. d The structure of an NPM monomer. The image shows the typical triangular cross-section and the arrangement of β-sheets in an NPM monomer

Fig. 4

The sequence alignment of putative plant nucleoplasmins with known nucleoplasmins. The sequences of the N-terminal core domains of HDTs and FKBP-nucleoplasmins from A. thaliana aligned with that of X. laevis nucleoplasmin, D. melanogaster nucleoplasmin-like protein, and D. melanogaster FKBP39 nucleoplasmin domain. The residues conserved across all the sequences are highlighted in yellow, residues conserved in at least five sequences are highlighted in cyan and the residues forming the acidic tract are shown in red. The β-sheet regions of known structures are labeled and underlined. The sequence alignment was done using the multiple sequence alignment tool ClustalW

Fig. 5

The domain organization of the FACT subunits from S. cerevisiae, H. sapiens, and A. thaliana. NTD, N-terminal domain; DD, dimerization domain; MD, middle domain; CTD, C-terminal domain; IDD, intrinsically disordered domain; CID, C-terminal intrinsically disordered domain; HMG, high mobility group domain

Fig. 6

FACT domain structures. a The structure of C. arietinum SPT16 NTD (PDB id, 5CE6). The important structural features are labeled. The K197 residue, which provides a hinge and separates the two domains, is represented in stick model in green and the LXXS loop in stick model and red. b The structural overlap of SPT16 NTDs from C. arietinum and S. cerevisiae (PDB id, 3BIT). C. arietinum SPT16 NTD is in blue and S. cerevisiae SPT16 NTD is in light pink. The r.m.s.d. of Cα atoms obtained after alignment was 1.94 Å. c The close-up view of histone interaction from the structure of S. cerevisiae SPT16-H2A-H2B complex (PDB id, 4WNN). H2B is in yellow, and H2A is in purple. The residues of H2B forming hydrophobic pocket are shown in stick representation and are labeled. The SPT16 NTD peptide is in stick representation in green, and all the residues are marked. d The structure overlap of AtSPT16 middle domain (pink) and HsSPT16 MD (yellow) (PDB id, 4Z2N). The r.m.s.d. of Cα atoms obtained after alignment was 1.94 Å. The conserved histone interacting residues in AtSPT16 are shown in stick model. e The structure of D. melanogaster SSRP1- HMG box domain (PDB id, 1WXL). The three helices that form the L-shaped fold, typical of HMGB domain are labeled