7W1Y

Human MCM double hexamer bound to natural DNA duplex (polyAT/polyTA)

これはPDB形式変換不可エントリーです。

7W1Y の概要

• エントリーDOI: 10.2210/pdb7w1y/pdb
• EMDBエントリー: 32258
• 分子名称: DNA replication licensing factor MCM2, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (12 entities in total)
• 機能のキーワード: replication, cell cycle-dna complex, cell cycle/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 1140056.77

構造登録者

Li, J.,Dong, J.,Dang, S.,Zhai, Y. (登録日: 2021-11-21, 公開日: 2023-02-08, 最終更新日: 2024-06-26)

主引用文献

Li, J.,Dong, J.,Wang, W.,Yu, D.,Fan, X.,Hui, Y.C.,Lee, C.S.K.,Lam, W.H.,Alary, N.,Yang, Y.,Zhang, Y.,Zhao, Q.,Chen, C.L.,Tye, B.K.,Dang, S.,Zhai, Y.
The human pre-replication complex is an open complex.
Cell, 186:98-111.e21, 2023

PubMed Abstract: In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome maintenance (MCM) 2-7 double hexamer (DH) to melt origin DNA strands. However, the mechanism for this initial melting is unknown. Here, we report a 2.59-Å cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as the pre-replication complex. In this structure, the hMCM-DH with a constricted central channel untwists and stretches the DNA strands such that almost a half turn of the bound duplex DNA is distorted with 1 base pair completely separated, generating an initial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibits DH formation and replication initiation. Mapping of hMCM-DH footprints indicates that IOSs are distributed across the genome in large clusters aligning well with initiation zones designed for stochastic origin firing. This work unravels an intrinsic mechanism that couples DH formation with initial DNA melting to license replication initiation in human cells.

PubMed: 36608662
DOI: 10.1016/j.cell.2022.12.008

実験手法

ELECTRON MICROSCOPY (2.59 Å)