Dynamics of the Nucleosome Core Particle Revealed from a New Database of High-Resolution X-Ray Crystallographic and Simulated Structures

Abstract

The nucleosome core particle is a highly conserved structure which can play diverse roles depending on the organism, cell, or part of chromatin in which it resides. The Protein Data Bank currently contains approximately 90 nucleosome core particle structures, most of which were determined in the last five years. The recent emergence of the field of epigenetics, and the increase in data available from experiments, warrants a need to develop new approaches to compare features of interest across multiple structures.The growing ensemble of structural data garnered from in vitro and in silico experiments provides a unique platform to study the mechanochemical properties of the nucleosome. We have developed a database and new computational tools to allow researchers to analyze and compare the nucleosome core particle structures deposited in the Protein Data Bank. The features of the DNA-protein assembly can be examined in novel coordinate frames placed on the structure, allowing researchers to obtain a better understanding of the organization and subtleties of the macromolecular complexes. This comparison allows one to examine the ‘motion’ of specific residues of interest, including specific sites of post-translational histone modification. The database also includes DNA-histone contact points, DNA conformational parameters, and information about protein features such as the secondary structure in the globular histone core and the ‘motion’ of the histone tails. Along with these features, we also characterize the dynamics of the global structure of the nucleosome core particle, including changes in the superhelical path of the DNA, rearrangements of the histone tetramers, and nucleosome stacking inside crystals. This information allows us to understand and model the critical role of mono-nucleosome structural propensity in processes such as carcinogenic modifications of the DNA, and nucleosome remodeling.