Arents G, Moudrianakis E N
Department of Biology, Johns Hopkins University, Baltimore, MD 21218.
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10489-93. doi: 10.1073/pnas.90.22.10489.
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.
核小体的组蛋白八聚体核心是由四个呈螺旋排列的组蛋白二聚体组成的蛋白质超螺旋结构。这个超螺旋结构的圆柱面由二聚体内和二聚体间的假二元轴标记，这些轴源于组蛋白折叠的性质。组蛋白折叠是“螺旋-链-螺旋”基序串联、平行重复的结果。由于这个基序出现在四个二聚体中，从而产生了重复的结构元件，即“平行β桥”和“螺旋I的配对末端”基序。八聚体表面大量的正电荷呈现为位于DNA预期路径上的左手螺旋。我们已将一部分DNA假二元轴与八聚体假二元轴进行匹配，从而构建了一个核小体模型。在该模型中，两条DNA链与组蛋白正电荷的路径重合，双螺旋的中间12圈在重复结构基序处与八聚体表面接触。这些互补接触的特性似乎解释了组蛋白对双螺旋DNA的偏好，并为核小体功能的变构调节提供了可能的基础。
