在可复制的六米酶中,DNA转位的机制
Eric J Enemark1, Leemor Joshua-Tor
1W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Nature
|July 21, 2006
概括
乳头瘤病毒E1螺旋酶用于DNA转位的独特阶梯机制. ATP水解驱动子单元的顺序运动,通过六合环转移单链DNA.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子病毒学分子病毒学
背景情况:
- 乳头瘤病毒E1蛋白质作为六环环化酶起作用.
- AAA+家族蛋白质E1对于病毒DNA复制至关重要.
- 通过E1对ATP依赖DNA转位的机制仍然不完全理解.
研究的目的:
- 阐明DNA转位与由乳头瘤病毒E1螺旋酶的ATP水解相结合的机制.
- 确定E1六合体中核酸依赖的构造变化的结构基础.
主要方法:
- 采用X射线晶体学,获得E1六合体的高分辨率结构.
- 结构被确定为复杂的单链DNA和各种核酸状态 (ATP,ADP,Apo).
主要成果:
- 晶体结构揭示了一个单一的DNA链绑在六合体通道内.
- 结合DNA的针头形成了一个螺旋楼梯,它与DNA骨干连续相互作用.
- E1子单元的独特结构构造与ATP,ADP和apo状态相关,与发针高度相关.
结论:
- 提出了一种逐步的DNA转位机制,由顺序的ATP水解和E1子单元的构造变化驱动.
- 每个子单元在ATP循环中进步,将其DNA结合的发针移动下楼梯以转移DNA.
- 在六边形环周围的这种协调作用促进了高效的单链DNA运动.
相关概念视频
The DNA Replication Fork
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
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DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
The Replisome
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
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Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
The DNA Replication Fork
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
The Replisome
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...


