Solution structure of the isolated histone H2A-H2B heterodimer

During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four alpha-helices and two beta-strands (alpha(1)-beta(1)-alpha(2)-beta 2-alpha(3)-alpha(C)), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal alpha(N) helix, C-terminal beta(3) strand, and 3(10) helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A alpha(1) and H2B alpha(C) helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {H-1}-N-15 hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 3(10) helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin.