Topography of the histone octamer surface: repeating structural motifs utilized in the docking of nucleosomal DNA

Abstract

The histone octamer core of the nucleosome is a protein superhelix of four spirally arrayed histone dimers. The cylindrical face of this superhelix is marked by intradimer and interdimer pseudodyad axes, which derive from the nature of the histone fold. The histone fold appears as the result of a tandem, parallel duplication of the "helix-strand-helix" motif. This motif, by its occurrence in the four dimers, gives rise to repetitive structural elements--i.e., the "parallel beta bridges" and the "paired ends of helix I" motifs. A preponderance of positive charges on the surface of the octamer appears as a left-handed spiral situated at the expected path of the DNA. We have matched a subset of DNA pseudodyads with the octamer pseudodyads and thus have built a model of the nucleosome. In it, the two DNA strands coincide with the path of the histone-positive charges, and the central 12 turns of the double helix contact the surface of the octamer at the repetitive structural motifs. The properties of these complementary contacts appear to explain the preference of histones for double-helical DNA and to suggest a possible basis for allosteric regulation of nucleosome function.