Structural Mechanisms of Histone Recognition by Histone Chaperones

Chromatin is the complex of DNA and proteins that comprises the physiological form of the genome. Non-covalent interactions between DNA and histone proteins are necessary to compact large eukaryotic genomes into relatively small cell nuclei. The nucleosome is the fundamental repeating unit of chromatin, and is composed of 147bp of DNA wrapped around an octamer of histone proteins: 2 copies of each H2A, H2B, H3 and H4.

Assembly of nucleosomes in the cell requires the coordinated effort of many proteins including ATP-dependent chromatin remodeling enzymes and ATP-independent histone chaperone proteins. Histone chaperones are a large class of proteins responsible for binding the highly basic histone proteins, shielding them from non-specific interactions, facilitating nuclear import of histones, and finally depositing histones onto DNA to form nucleosomes. Despite performing many overlapping functions, histone chaperone proteins are highly structurally divergent. However, nearly all histone chaperones contain highly charged intrinsically disordered regions (IDRs)1. In many cases truncation of these conserved regions results in loss of histone affinity and deposition functions.

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Image: (extract) SAXS analysis of Npm Core+A2 truncation (1-145) bound to five H2A/H2B dimers. Left: small angle x-ray scattering curve of the complex (purple dots). Simulated SAXS curve from the best scoring structural model shown as a black line. Right: SAXS envelope of the complex (pink) with the best scoring structural model inside. Positioning of H2A/H2B dimers by NMR and SAXS structural restraints. Full image here.