Tne initiator of chromosomal DNA replication in E. coli.

大肠杆菌中染色体 DNA 复制的引发剂。

• 批准号: 11470486
• 负责人: TSUCHIYA Tomofusa
• 金额: $ 7.87万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470486/
• 关键词: DNA replication; DnaA; ADP; ATP; regulation of activity; ATPase; リン脂質; ORC; 酸性リン脂質; 機能ドメイン; 結晶構造解析; 癌; 開始因子; ATP結合; Cdc6p

DnaA protein, the initiator for chromosomal DNA replication in Escherichia coli, has various activities, such as oligomerization (DnaA-DnaA interaction), ATP binding. ATPase activity and membrane-binding. Site-directed mutational analyses have revealed not only the amino acid residues that are essential for these activities but also the functions of these activities. Following is a summary of the functions and regulatory mechanisms of DnaA protein in the initiation of chromosomal DNA replication. ATP-bound DnaA protein, but not other forms of the protein binds to the origin of DNA replication and forms oligomers to open-up the duplex DNA. This oligomerization is mediated by a DnaA-DnaA interaction through the N-terminal region of the protein. Alter initiation of DNA replication, the ATPase activity of DnaA protein is stimulated and DnaA protein is inactivated to the ADP-bound form to suppress the re-initiation of DNA replication. DnaA protein binds to acidic phospholipids through an ionic interaction between basic amino acid residues of the protein and acidic residues of phospholipids. This interaction seems to be involved in the re-activation of DnaA protein (from the ADP-bound form to the ATP-bound form) to initiate DNA replication after the appropriate interval.

DnaA蛋白是大肠杆菌染色体DNA复制的启动剂，具有多种活性，如寡聚（DNA -DnaA相互作用）、ATP结合等。atp酶活性与膜结合。位点突变分析不仅揭示了这些活性所必需的氨基酸残基，而且揭示了这些活性的功能。以下是DNA蛋白在染色体DNA复制起始中的功能和调控机制的综述。atp结合的DNA蛋白质，而不是其他形式的蛋白质，与DNA复制的起点结合，形成寡聚物，打开双链DNA。这种寡聚化是通过蛋白质n端区域的dna - dna相互作用介导的。DNA复制开始后，DNA蛋白的atp酶活性受到刺激，DNA蛋白被灭活为adp结合形式，从而抑制DNA复制的重新开始。dna蛋白通过蛋白质的碱性氨基酸残基和磷脂的酸性残基之间的离子相互作用与酸性磷脂结合。这种相互作用似乎涉及DNA蛋白的再激活（从adp结合形式到atp结合形式），以在适当的间隔后启动DNA复制。

项目成果

Makise, M.: "Sequence-independent DNA binding activity of DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli"J.Biochem.. 131. 419-425 (2002)

Makise, M.：“DnaA 蛋白的序列独立 DNA 结合活性，大肠杆菌中染色体 DNA 复制的起始因子”J.Biochem.. 131. 419-425 (2002)

Takahashi. N.: "Functions of sensor 1 and sensor 2 regions of Saccharomyces cerevisiae Cdc6p in vivo and in vitro"J.Biol.Chem.. 277. 16033-16040 (2002)

高桥。

Yamaguchi, Y., et al.: "Involvement of Arg-328, Arg-334, and Arg-342 of DnaA protein in the functional interaction with acidic phospholipids"Biochem. J.. 340. 433-438 (1999)

Yamaguchi，Y.，等人：“DnaA 蛋白的 Arg-328、Arg-334 和 Arg-342 在与酸性磷脂的功能性相互作用中的参与”Biochem。

Makise, M.: "Identification of amino acids involved in the functional interaction between DnaA protein and acidic phospholipids"J.Biol.Chem.. 275. 4513-4518 (2000)

Makise, M.：“鉴定参与 DnaA 蛋白和酸性磷脂之间功能相互作用的氨基酸”J.Biol.Chem.. 275. 4513-4518 (2000)

Yamaguchi, Y.: "Involvement of Arg-328, Arg-334, and Arg-342 of DnaA protein in the functional interaction with acidic phospholipids"Biochem. J.. 340. 433-438 (1999)

Yamaguchi, Y.：“DnaA 蛋白的 Arg-328、Arg-334 和 Arg-342 在与酸性磷脂的功能性相互作用中的参与”Biochem。