7EPU

Crystal structure of HsALC1

7EPU の概要

• エントリーDOI: 10.2210/pdb7epu/pdb
• 分子名称: non-immunized human scFv, Chromodomain-helicase-DNA-binding protein 1-like, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: macrodomain, autoinhibition, dna damage, parp1, motor protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 127613.07

構造登録者

Wang, L.,Chen, K.J. (登録日: 2021-04-27, 公開日: 2021-07-14, 最終更新日: 2025-09-17)

主引用文献

Wang, L.,Chen, K.,Chen, Z.
Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome.
Nat Commun, 12:4057-4057, 2021

PubMed Abstract: Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer.

PubMed: 34210977
DOI: 10.1038/s41467-021-24320-4

実験手法

X-RAY DIFFRACTION (3.5 Å)