8THU

Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1

8THU の概要

• エントリーDOI: 10.2210/pdb8thu/pdb
• EMDBエントリー: 41272
• 分子名称: Histone H2A.Z, Histone H3.2, Histone H4, ... (6 entities in total)
• 機能のキーワード: chromatin, histone h4 modification, methyltransferase, gene regulation, gene regulation-dna complex, gene regulation/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 198001.63

構造登録者

Abini-Agbomson, S.,Armache, K.-J. (登録日: 2023-07-18, 公開日: 2023-09-06, 最終更新日: 2025-05-21)

主引用文献

Abini-Agbomson, S.,Gretarsson, K.,Shih, R.M.,Hsieh, L.,Lou, T.,De Ioannes, P.,Vasilyev, N.,Lee, R.,Wang, M.,Simon, M.D.,Armache, J.P.,Nudler, E.,Narlikar, G.,Liu, S.,Lu, C.,Armache, K.J.
Catalytic and non-catalytic mechanisms of histone H4 lysine 20 methyltransferase SUV420H1.
Mol.Cell, 83:2872-2883.e7, 2023

PubMed Abstract: SUV420H1 di- and tri-methylates histone H4 lysine 20 (H4K20me2/H4K20me3) and plays crucial roles in DNA replication, repair, and heterochromatin formation. It is dysregulated in several cancers. Many of these processes were linked to its catalytic activity. However, deletion and inhibition of SUV420H1 have shown distinct phenotypes, suggesting that the enzyme likely has uncharacterized non-catalytic activities. Our cryoelectron microscopy (cryo-EM), biochemical, biophysical, and cellular analyses reveal how SUV420H1 recognizes its nucleosome substrates, and how histone variant H2A.Z stimulates its catalytic activity. SUV420H1 binding to nucleosomes causes a dramatic detachment of nucleosomal DNA from the histone octamer, which is a non-catalytic activity. We hypothesize that this regulates the accessibility of large macromolecular complexes to chromatin. We show that SUV420H1 can promote chromatin condensation, another non-catalytic activity that we speculate is needed for its heterochromatin functions. Together, our studies uncover and characterize the catalytic and non-catalytic mechanisms of SUV420H1, a key histone methyltransferase that plays an essential role in genomic stability.

PubMed: 37595555
DOI: 10.1016/j.molcel.2023.07.020

実験手法

ELECTRON MICROSCOPY (3.1 Å)