8SIY

Origin Recognition Complex Associated (ORCA) protein bound to H4K20me3-nucleosome

8SIY の概要

• エントリーDOI: 10.2210/pdb8siy/pdb
• 関連するPDBエントリー: 8SIU
• EMDBエントリー: 40522
• 分子名称: Leucine-rich repeat and WD repeat-containing protein 1, Histone H3.2, Histone H4, ... (8 entities in total)
• 機能のキーワード: chromatin binding, orc binding, nucleosome, replication
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 285906.37

構造登録者

Bleichert, F.,Ekundayo, B.E. (登録日: 2023-04-17, 公開日: 2023-08-02, 最終更新日: 2024-11-06)

主引用文献

Sahu, S.,Ekundayo, B.E.,Kumar, A.,Bleichert, F.
A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin.
Embo J., 42:e114654-e114654, 2023

PubMed Abstract: Eukaryotic cells use chromatin marks to regulate the initiation of DNA replication. The origin recognition complex (ORC)-associated protein ORCA plays a critical role in heterochromatin replication in mammalian cells by recruiting the initiator ORC, but the underlying mechanisms remain unclear. Here, we report crystal and cryo-electron microscopy structures of ORCA in complex with ORC's Orc2 subunit and nucleosomes, establishing that ORCA orchestrates ternary complex assembly by simultaneously recognizing a highly conserved peptide sequence in Orc2, nucleosomal DNA, and repressive histone trimethylation marks through an aromatic cage. Unexpectedly, binding of ORCA to nucleosomes prevents chromatin array compaction in a manner that relies on H4K20 trimethylation, a histone modification critical for heterochromatin replication. We further show that ORCA is necessary and sufficient to specifically recruit ORC into chromatin condensates marked by H4K20 trimethylation, providing a paradigm for studying replication initiation in specific chromatin contexts. Collectively, our findings support a model in which ORCA not only serves as a platform for ORC recruitment to nucleosomes bearing specific histone marks but also helps establish a local chromatin environment conducive to subsequent MCM2-7 loading.

PubMed: 37551430
DOI: 10.15252/embj.2023114654

実験手法

ELECTRON MICROSCOPY (2.9 Å)