5GTC

Crystal structure of complex between DMAP-SH conjugated with a Kaposi's sarcoma herpesvirus LANA peptide (5-15) and nucleosome core particle

5GTC の概要

• エントリーDOI: 10.2210/pdb5gtc/pdb
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (8 entities in total)
• 機能のキーワード: dna binding, nucleus, histone fold, chromatin formation, nucleosome, structural protein-dna complex, structural protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: P68431 P62805 P04908 P06899
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 203880.50

構造登録者

Arimura, Y.,Kato, D.,Suto, H.,Kurumizaka, H.,Kawashima, S.A.,Yamatsugu, K.,Kanai, M. (登録日: 2016-08-19, 公開日: 2017-06-28, 最終更新日: 2024-11-13)

主引用文献

Amamoto, Y.,Aoi, Y.,Nagashima, N.,Suto, H.,Yoshidome, D.,Arimura, Y.,Osakabe, A.,Kato, D.,Kurumizaka, H.,Kawashima, S.A.,Yamatsugu, K.,Kanai, M.
Synthetic Posttranslational Modifications: Chemical Catalyst-Driven Regioselective Histone Acylation of Native Chromatin.
J. Am. Chem. Soc., 139:7568-7576, 2017

PubMed Abstract: Posttranslational modifications (PTMs) of histones play an important role in the complex regulatory mechanisms governing gene transcription, and their dysregulation can cause diseases such as cancer. The lack of methods for site-selectively modifying native chromatin, however, limits our understanding of the functional roles of a specific histone PTM, not as a single mark, but in the intertwined PTM network. Here, we report a synthetic catalyst DMAP-SH (DSH), which activates chemically stable thioesters (including acetyl-CoA) under physiological conditions and transfers various acyl groups to the proximate amino groups. Our data suggest that DSH, conjugated with a nucleosome ligand, such as pyrrole-imidazole-polyamide and LANA (latency-associated nuclear antigen)-peptide, promotes both natural (including acetylation, butyrylation, malonylation, and ubiquitination) and non-natural (azido- and phosphoryl labeling) PTMs on histones in recombinant nucleosomes and/or in native chromatin, at lysine residues close to the DSH moiety. To investigate the validity of our method, we used LANA-DSH to promote histone H2B lysine-120 (K120) acylation, the function of which is largely unknown. H2BK120 acetylation and malonylation modulated higher-order chromatin structures by reducing internucleosomal interactions, and this modulation was further enhanced by histone tail acetylation. This approach, therefore, may have versatile applications for dissecting the regulatory mechanisms underlying chromatin function.

PubMed: 28534629
DOI: 10.1021/jacs.7b02138

実験手法

X-RAY DIFFRACTION (2.7 Å)