7V3U

Cryo-EM structure of MCM double hexamer with structured Mcm4-NSD

これはPDB形式変換不可エントリーです。

7V3U の概要

• エントリーDOI: 10.2210/pdb7v3u/pdb
• EMDBエントリー: 31684
• 分子名称: DNA replication licensing factor MCM2, ADENOSINE-5'-DIPHOSPHATE, DNA replication licensing factor MCM3, ... (10 entities in total)
• 機能のキーワード: dna replication initiation, complex, replicative helicase, replication, cell cycle
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 1219771.11

構造登録者

Cheng, J.,Li, N.,Huo, Y.,Dang, S.,Tye, B.,Gao, N.,Zhai, Y. (登録日: 2021-08-11, 公開日: 2022-04-13, 最終更新日: 2025-07-02)

主引用文献

Cheng, J.,Li, N.,Huo, Y.,Dang, S.,Tye, B.K.,Gao, N.,Zhai, Y.
Structural Insight into the MCM double hexamer activation by Dbf4-Cdc7 kinase.
Nat Commun, 13:1396-1396, 2022

PubMed Abstract: The Dbf4-dependent kinase Cdc7 (DDK) regulates DNA replication initiation by phosphorylation of the MCM double hexamer (MCM-DH) to promote helicase activation. Here, we determine a series of cryo electron microscopy (cryo-EM) structures of yeast DDK bound to the MCM-DH. These structures, occupied by one or two DDKs, differ primarily in the conformations of the kinase core. The interactions of DDK with the MCM-DH are mediated exclusively by subunit Dbf4 straddling across the hexamer interface on the three N-terminal domains (NTDs) of subunits Mcm2, Mcm6, and Mcm4. This arrangement brings Cdc7 close to its only essential substrate, the N-terminal serine/threonine-rich domain (NSD) of Mcm4. Dbf4 further displaces the NSD from its binding site on Mcm4-NTD, facilitating an immediate targeting of this motif by Cdc7. Moreover, the active center of Cdc7 is occupied by a unique Dbf4 inhibitory loop, which is disengaged when the kinase core assumes wobbling conformations. This study elucidates the versatility of Dbf4 in regulating the ordered multisite phosphorylation of the MCM-DH by Cdc7 kinase during helicase activation.

PubMed: 35296675
DOI: 10.1038/s41467-022-29070-5

実験手法

ELECTRON MICROSCOPY (3.2 Å)