The N-terminal Tails of Histones H2A and H2B Adopt Two Distinct Conformations in the Nucleosome with Contact and Reduced Contact to DNA. Issue 15 (23rd July 2021)

• Record Type: Journal Article
• Authors: Ohtomo, Hideaki; Kurita, Jun-ichi; Sakuraba, Shun; Li, Zhenhai; Arimura, Yasuhiro; Wakamori, Masatoshi; Tsunaka, Yasuo; Umehara, Takashi; Kurumizaka, Hitoshi; Kono, Hidetoshi; Nishimura, Yoshifumi
• Is Part Of: Journal of molecular biology. Volume 433:Issue 15(2021)
• Publication Date: 2021-07-23
• Subjects: histone tail -- intrinsically disordered region -- NMR -- molecular dynamics simulation -- protein-DNA interaction; HSQC heteronuclear single-quantum coherence spectroscopy -- NOE nuclear Overhauser effect -- cryo-EM cryogenic electron microscopy -- MD Molecular dynamics -- DSB double strand break -- HDX-MS hydrogen/deuterium exchange mass spectrometry -- HBOND hydrogen bond; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167110
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: NMR characterization of H2A-H2B tails in the nucleosome with and without linker DNA. The linker DNA affects the conformation of the H2A C-tail in the nucleosome. NMR and MD reveal distinct conformations of both H2A N-tails and both H2B N-tails. Both N-tails appeared to adopt a DNA-contact and a reduced-contact conformation. The H2A N-tail conformation likely depends on the H2B N-tail conformation. Abstract: The nucleosome comprises two histone dimers of H2A-H2B and one histone tetramer of (H3-H4)2, wrapped around by ~145 bp of DNA. Detailed core structures of nucleosomes have been established by X-ray and cryo-EM, however, histone tails have not been visualized. Here, we have examined the dynamic structures of the H2A and H2B tails in 145-bp and 193-bp nucleosomes using NMR, and have compared them with those of the H2A and H2B tail peptides unbound and bound to DNA. Whereas the H2A C-tail adopts a single but different conformation in both nucleosomes, the N-tails of H2A and H2B adopt two distinct conformations in each nucleosome. To clarify these conformations, we conducted molecular dynamics (MD) simulations, which suggest that the H2A N-tail can locate stably in either the major or minor grooves of nucleosomal DNA. While the H2B N-tail, which sticks out between two DNA gyres in the nucleosome, was considered to adopt two different orientations, one toward the entry/exit side and one on the opposite side. Then, the H2A N-tail minor groove conformation was obtained in the H2B opposite side and the H2B N-tail interacts with DNA similarly in both sides, though more varied conformations are obtained in the entry/exit side. Collectively, the NMR findings and MD simulations suggest that the minor groove conformer of the H2A N-tail is likely to contact DNA more strongly than the major groove conformer, and the H2A N-tail reduces contact with DNA in the major groove when the H2B N-tail is located in the entry/exit side.