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Structure of the eukaryotic MCM complex at 3.8 angstrom

机译：3.8埃的真核MCM复合物的结构

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摘要

DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior beta-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
机译：真核生物中的DNA复制受到多种机制的严格调控。此复制的中心步骤是在G1阶段的复制起点将异六聚体微染色体维持（MCM2-7）解旋酶复合物组装成无活性的双六聚体。在这里，使用冷冻电子显微镜，我们报告了从酵母G1染色质纯化的MCM2-7双六聚体的近原子结构。我们的结构表明，通过相互交叉的氨基末端结构域相互作用以倾斜和扭曲的方式排列的两个单个六聚体形成了一个弯曲的中央通道。由两个单一六聚体的保守内部β-发夹组成的四个缩环形成了一条狭窄通道，该通道紧密适合双链DNA。该狭窄的通道由双六聚体界面处的两个单六聚体的偏移加强，两侧是两对形成门的亚基MCM2和MCM5。扭曲和倾斜的单个六聚体的这些不同寻常的特征提示了一种融化原始DNA的协调机制，这需要中间DNA发生结构变形。

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  • 来源
    《Nature》 |2015年第7564期|186-191|共6页
  • 作者

    Li Ningning; Zhai Yuanliang; Zhang Yixiao; Li Wanqiu; Yang Maojun; Lei Jianlin; Tye Bik-Kwoon; Gao Ning;

  • 作者单位

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Kowloon, Hong Kong, Peoples R China|Hong Kong Univ Sci & Technol, Inst Adv Study, Kowloon, Hong Kong, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Kowloon, Hong Kong, Peoples R China|Cornell Univ, Dept Mol Biol & Genet, Coll Agr & Life Sci, Ithaca, NY 14853 USA;

    Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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