The structure of bacterial DnaA: implications for general mechanisms underlying DNA replication initiation
The structure of bacterial DnaA: implications for general mechanisms underlying DNA replication initiation
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DOI：
10.1093/emboj/cdf496
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发表时间：
2002-09-16
期刊：
影响因子：
11.4
通讯作者：
Berger, JM
中科院分区：
文献类型：
--
作者：
Erzberger, JP;Pirruccello, MM;Berger, JM
DNA复制的启动是所有生物体细胞周期中的关键事件。在细菌中，复制起始发生在特定的起始序列处，该起始序列被起始蛋白 DnaA 的寡聚复合物识别和加工。我们已经以 2.7 埃的分辨率确定了 Aquifex aeolicus DnaA 蛋白保守核心的结构。该蛋白质包含 AAA+ 核苷酸结合折叠，通过长螺旋连接器连接到全螺旋 DNA 结合结构域。该结构可作为理解各种 DnaA 突变的物理后果的模板，并且蛋白质中的保守基序表明起源加工的两个关键方面（DNA 结合和同源寡聚化）是如何介导的。 DnaA 中这些基序的空间排列与真核类古菌复制起始因子 Cdc6/Orc1 的空间排列相似，表明起源加工的机械元件可能在细菌、古菌和真核生命领域中是保守的。
The initiation of DNA replication is a key event in the cell cycle of all organisms. In bacteria, replication initiation occurs at specific origin sequences that are recognized and processed by an oligomeric complex of the initiator protein DnaA. We have determined the structure of the conserved core of the Aquifex aeolicus DnaA protein to 2.7 Angstrom resolution. The protein comprises an AAA+ nucleotide-binding fold linked through a long, helical connector to an all-helical DNA-binding domain. The structure serves as a template for understanding the physical consequences of a variety of DnaA mutations, and conserved motifs in the protein suggest how two critical aspects of origin processing, DNA binding and homo-oligomerization, are mediated. The spatial arrangement of these motifs in DnaA is similar to that of the eukaryotic-like archaeal replication initiation factor Cdc6/Orc1, demonstrating that mechanistic elements of origin processing may be conserved across bacterial, archaeal and eukaryotic domains of life.