全长CRESS-DNA复制酶的动力学和形状
Elvira Tarasova1, Reza Khayat1
1Department of Chemistry and Biochemistry, City College of New York, New York, NY 10031, USA.
Viruses
|December 23, 2023
概括
分子动力学模拟揭示了循环Rep编码单链DNA (CRESS-DNA) 病毒的Replicase (Rep) 蛋白如何沿着单链DNA移动. 这些发现澄清了病毒复制的机制,并指导了未来对Rep的研究.
科学领域:
- 结构生物学和病毒学.
- 病毒蛋白的分子动力学模拟.
背景情况:
- 循环复制编码单链DNA (CRESS-DNA) 病毒利用复制酶 (Rep) 蛋白进行复制.
- Rep是一种具有内核酶,寡合酶和ATPase域 (ED,OD,AD) 的基酶.
- 之前的冷EM研究揭示了PCV2 Rep结构,六合体形成,ssDNA/核酸结合和AD楼梯排列,这表明了手对手转位机制.
研究的目的:
- 通过CRESS-DNARep的ATPase域 (AD) 对ssDNA转位的拟议的交换机制进行仔细检查.
- 通过全原子分子动力学 (MD) 模拟,研究不同状态的Rep动力学.
- 了解ssDNA和ADP在稳定AD楼梯结构中的作用.
主要方法:
- 全原子分子动力学 (MD) 模拟PCV2 Rep蛋白.
- 对三个条件进行了模拟:使用ssDNA和ADP进行Rep,使用ssDNA进行Rep,单独使用Rep.
- 每个模拟运行了700纳秒,在200纳秒内观察到收.
主要成果:
- MD模拟提供了关于Rep的动态及其与ssDNA和ADP的相互作用的见解.
- 模拟表明ssDNA和ADP在驱动AD采用楼梯形状时的重要性.
- 这项研究代表了CRESS-DNA Rep蛋白的第一个全原子MD模拟.
结论:
- 该研究验证了Rep及其组件在不同约束条件下的动态行为.
- 这些发现支持ssDNA转移的拟议的交换机制,由核酸结合和水解驱动.
- 这项工作为未来的MD研究奠定了基础,以阐明Rep介导DNA转位的化学机制.
相关概念视频
The Replisome
33.5K
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 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...
33.5K
DNA Helicases
21.3K
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...
21.3K
The DNA Replication Fork
36.0K
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...
36.0K
Replication in Eukaryotes
170.8K
Overview
170.8K
DNA Topoisomerases
31.3K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.3K
Replication in Prokaryotes
24.9K
DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
24.9K


