8SIY
Origin Recognition Complex Associated (ORCA) protein bound to H4K20me3-nucleosome
Summary for 8SIY
| Entry DOI | 10.2210/pdb8siy/pdb |
| Related | 8SIU |
| EMDB information | 40522 |
| Descriptor | Leucine-rich repeat and WD repeat-containing protein 1, Histone H3.2, Histone H4, ... (8 entities in total) |
| Functional Keywords | chromatin binding, orc binding, nucleosome, replication |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 12 |
| Total formula weight | 285906.37 |
| Authors | Bleichert, F.,Ekundayo, B.E. (deposition date: 2023-04-17, release date: 2023-08-02, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 37551430DOI: 10.15252/embj.2023114654 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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