Cryo-EM structure of human hexameric MCM2-7 complex

Naining Xu; Qingpeng Lin; Honglei Tian; Changdong Liu; Peiyi Wang; Ching Monica Suen; Hongyu Yang; Ye Xiang; Guang Zhu

doi:10.1016/j.isci.2022.104976

Cryo-EM structure of human hexameric MCM2-7 complex

iScience. 2022 Aug 17;25(9):104976. doi: 10.1016/j.isci.2022.104976. eCollection 2022 Sep 16.

Authors

Naining Xu^{1

2}, Qingpeng Lin³, Honglei Tian², Changdong Liu^{2

4}, Peiyi Wang⁵, Ching Monica Suen², Hongyu Yang¹, Ye Xiang³, Guang Zhu^{2

4

6}

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Stomatological Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
² Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 00000, China.
³ Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
⁴ HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China.
⁵ Cryo-EM Center of SUSTech, Southern University of Science and Technology, Shenzhen 518055, China.
⁶ State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 00000, China.

Abstract

The central step in the initiation of eukaryotic DNA replication is the loading of the minichromosome maintenance 2-7 (MCM2-7) complex, the core of the replicative DNA helicase, onto chromatin at replication origin. Here, we reported the cryo-EM structure of endogenous human single hexameric MCM2-7 complex with a resolution at 4.4 Å, typically an open-ring hexamer with a gap between Mcm2 and Mcm5. Strikingly, further analysis revealed that human MCM2-7 can self-associate to form a loose double hexamer which potentially implies a novel mechanism underlying the MCM2-7 loading in eukaryote. The high-resolution cryo-EM structure of human MCM2-7 is critical for understanding the molecular mechanisms governing human DNA replication, especially the MCM2-7 chromatin loading and pre-replicative complex assembly.

Keywords: Cell biology; Molecular biology; Structural biology.