NucleosomeDB - a database of 3D nucleosome structures and their complexes with comparative analysis toolkit

Abstract

Nucleosomes are basic building blocks of chromatin, comprising DNA wrapped around an octamer of eight histone proteins. They play key roles in DNA compaction, epigenetic mark up of the genome and actively participate in chromatin dynamics. X-ray and later cryo-EM studies have contributed greatly to our understanding of nucleosome structure, their interactions and dynamics. With over 470 nucleosome containing structures in the Protein Data Bank there is a wealth of information to be gleaned from these structures, especially through comparative analysis. However, due to the variability in their representation (chain naming, residue numbering, other artifacts), these structures cannot be systematically analyzed "as is". To address this issue, we developed a framework for analyzing and classifying nucleosome structures and their complexes, resulting in the creation of the NucleosomeDB database and the corresponding web-service. NucleosomeDB allows researchers to search, explore, and compare nucleosomes with each other, despite differences in composition and peculiarities of their representation. By utilizing the information contained within the NucleosomeDB, researchers can gain valuable insights into how nucleosomes interact with DNA and other proteins, assess the implications of mutations and protein binding on nucleosome structure. The detailed information contained within NucleosomeDB can contribute to a better understanding of the structure and function of nucleosomes, and ultimately, the functioning of chromatin and gene regulation. NucleosmeDB is freely available at https://nucldb.intbio.org.

Deciphering principles of nucleosome interactions and impact of cancer-associated mutations from comprehensive interaction network analysis

“…Last, using the annotations from NucleosomeDB database [ 21 ], we have categorized all nucleosome complex structures into 20 types based on the functions of nucleosome binding partners and then compared their binding modes across different functional types ( Figure 6 ). Our results indicate that among the different functional classes, chromatin factors target nucleosome through both common and unique binding hotspots.…”

“…The UniProt IDs of all binding proteins were subjected to the webserver ( https://www.pantherdb.org ) for functional classification using the PATHER protein class [ 35 , 36 ]. For identified 83 representative nucleosome complex structures, we have classified them into 20 categories using the functional annotations from NucleosomeDB database [ 21 ] ( Supplementary Table 7 ) .…”

“…These structures provide comprehensive information of histone interactions at the atomic level and enable characterizations of histone/nucleosome binding interfaces at atomic resolution [ 20 ]. One recent computational study has developed a framework for systematical analysis and classification of nucleosome structures and their complexes [ 21 ]. NucPosDB reports various experimental nucleosome maps across different cell types and software for computational analysis of nucleosome positioning and occupancy [ 22 ].…”

Interactions of Nucleosomes with Acidic Patch-Binding Peptides: A Combined Structural Bioinformatics, Molecular Modeling, Fluorescence Polarization, and Single-Molecule FRET Study

“…Using the nucleosome database (NuclDB, http://nucldb.intbio.org (accessed on 24 September 2023), [67]), we have aligned and extracted all the structures containing nucleosomes bound to other interactors (proteins or peptides) from the PDB database, available as of 08/24/2023. All structures were superimposed with the reference structure (PDB ID 1KX5) by sequence-structure alignments using in-house Python scripts.…”