Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
Protein Sci. 2019 Jun;28(6):990-1004. doi: 10.1002/pro.3615. Epub 2019 Apr 17.
DNA replication mechanisms are conserved across all organisms. The proteins required to initiate, coordinate, and complete the replication process are best characterized in model organisms such as Escherichia coli. These include nucleotide triphosphate-driven nanomachines such as the DNA-unwinding helicase DnaB and the clamp loader complex that loads DNA-clamps onto primer-template junctions. DNA-clamps are required for the processivity of the DNA polymerase III core, a heterotrimer of α, ε, and θ, required for leading- and lagging-strand synthesis. DnaB binds the DnaG primase that synthesizes RNA primers on both strands. Representative structures are available for most classes of DNA replication proteins, although there are gaps in our understanding of their interactions and the structural transitions that occur in nanomachines such as the helicase, clamp loader, and replicase core as they function. Reviewed here is the structural biology of these bacterial DNA replication proteins and prospects for future research.
DNA 复制机制在所有生物体中都被保守。启动、协调和完成复制过程所需的蛋白质在模式生物如大肠杆菌中得到了最好的描述。这些蛋白质包括核苷酸三磷酸驱动的纳米机器，如 DNA 解旋酶 DnaB 和加载 DNA 夹到引物-模板连接处的夹取器复合物。DNA 夹对于 DNA 聚合酶 III 核心的持续性是必需的，该核心是 α、ε 和 θ 的异三聚体，用于前导链和滞后链的合成。DnaB 结合 DnaG 引发酶，该酶在两条链上合成 RNA 引物。大多数类别的 DNA 复制蛋白都有代表性结构，但我们对它们的相互作用以及在解旋酶、夹取器复合物和复制酶核心等纳米机器中发生的结构转变的理解仍存在空白，这些纳米机器在发挥功能时会发生这些转变。本文综述了这些细菌 DNA 复制蛋白的结构生物学及其未来研究前景。
