9BCX

Cryo-EM structure of the S. cerevisiae ORC-Cdc6-Mcm2-7-DNA complex with a fully closed Mcm2-Mcm5 DNA entry gate

これはPDB形式変換不可エントリーです。

9BCX の概要

• エントリーDOI: 10.2210/pdb9bcx/pdb
• EMDBエントリー: 44441
• 分子名称: DNA replication licensing factor MCM2, Origin recognition complex subunit 4, Origin recognition complex subunit 5, ... (18 entities in total)
• 機能のキーワード: dna replication, cryo-em, occm-deltac6, replication-dna complex, dna binding protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 1173128.88

構造登録者

Yuan, Z.,Bai, L.,Li, H.,Speck, C. (登録日: 2024-04-10, 公開日: 2025-01-01, 最終更新日: 2025-01-15)

主引用文献

Faull, S.V.,Barbon, M.,Mossler, A.,Yuan, Z.,Bai, L.,Reuter, L.M.,Riera, A.,Winkler, C.,Magdalou, I.,Peach, M.,Li, H.,Speck, C.
MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.
Nat Commun, 16:14-14, 2025

PubMed Abstract: The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase.

PubMed: 39747125
DOI: 10.1038/s41467-024-55479-1

実験手法

ELECTRON MICROSCOPY (6.1 Å)