THE HISTONE FOLD - A UBIQUITOUS ARCHITECTURAL MOTIF UTILIZED IN DNA COMPACTION AND PROTEIN DIMERIZATION

The histones of all eukaryotes show only a low degree of primary structure homology, but our earlier crystallographic results defined a three-dimensional structural motif, the histone fold, common to all core histones, We now examine the specific architectural patterns within the fold and analyze the nature of the amino acid residues within its functional segments. The histone fold emerges as a fundamental protein dimerization motif while the differentiations of the tips of the histone dimers appear to provide the rules of core octamer assembly and the basis for nucleosome regulation. We present evidence for the occurrence of the fold from archaebacteria to mammals and propose the use of this structural motif to define a distinct family of proteins, the histone fold superfamily. It appears that evolution has conserved the conformation of the fold even through variations in primary structure and among proteins with various functional roles

TOPOGRAPHY OF THE HISTONE OCTAMER SURFACE - REPEATING STRUCTURAL MOTIFS UTILIZED IN THE DOCKING OF NUCLEOSOMAL DNA

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

THE NUCLEOSOMAL CORE HISTONE OCTAMER AT 3.1-A RESOLUTION - A TRIPARTITE PROTEIN ASSEMBLY AND A LEFT-HANDED SUPERHELIX

The structure of the octameric histone core of the nucleosome has been determined by x-ray crystallography to a resolution of 3.1 angstrom. The histone octamer is a tripartite assembly in which a centrally located (H3-H4)2 tetramer is flanked by two H2A-H2B dimers. It has a complex outer surface; depending on the perspective, the structure appears as a wedge or as a flat disk. The disk represents the planar projection of a left-handed proteinaceous superhelix with almost-equal-to 28 angstrom pitch. The diameter of the particle is 65 angstrom and the length is 60 angstrom at its maximum and almost-equal-to 10 angstrom at its minimum extension; these dimensions are in agreement with those reported earlier by Klug et al. [Klug, A., Rhodes, D., Smith, J., Finch, J. T. & Thomas, J. O. (1980) Nature (London) 287, 509-516]. The folded histone chains are elongated rather than globular and are assembled in a characteristic “handshake” motif. The individual polypeptides share a common central structural element of the helix-loop-helix type, which we name the histone fold