The Recognition Specificity of the CHD1 Chromodomain with Modified Histone H3 Peptides

摘要

Histone tail peptides comprise the flexible portion of chromatin, the substance which serves as the packaging for the eukaryotic genome. According to the histone code hypothesis, reader protein domains (chromodomains) can recognize modifications of amino acid residues within these peptides, regulating the expression of genes. We have performed simulations on models of CHD1 chromodomain complexed with a variety of histone H3 modifications. Binding free energies for both the overall complexes and individual residues within the protein and peptides were computed with MM-GBSA. The simulation results agree well with experimental data and identify several CHD1 residues that play key roles in the interaction with each of the H3 modifications. We identified one class of protein residues that bind to H3 in all of the complexes, and a second class of residues that bind only to particular H3 modifications. Additionally, we found that modifications of H3R2 and H3T3 have a dominant effect on the binding affinity; methylation of H3K4 has little effect on the interaction strength when H3R2 or H3T3 is modified. Our findings with regard to the specificity shown by the latter class of protein residues in their binding affinity to certain modifications of H3 support the histone code hypothesis.