在SARS-CoV-2复制-转录复合体中,酶-聚合酶合的结构基础
James Chen1, Brandon Malone1, Eliza Llewellyn1
1Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065, USA.
Cell
|August 14, 2020
概括
研究人员用nsp13螺旋酶可视化了SARS-CoV-2依赖RNA的RNA聚合酶 (RdRp) 复合体. 这种结构洞察力揭示了螺旋酶如何与RdRp相互作用,这对病毒复制和COVID-19药物开发至关重要.
科学领域:
- 结构生物学
- 病毒学
- 病毒复制的分子机制
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 是导致COVID-19大流行的原因.
- 病毒复制依赖于依赖于RNA的RNA聚合酶 (RdRp) 和nsp13螺旋酶等辅助因子.
- RdRp和nsp13都对病毒复制至关重要,并且是抗病毒疗法的关键目标.
研究的目的:
- 确定与nsp13螺旋酶复合的SARS-CoV-2全-RdRp的冷电子显微结构.
- 阐明 nsp13 螺旋酶与 holo-RdRp 复合体之间的相互作用接口.
- 确定抗病毒药物开发的潜在新目标.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得高分辨率的结构.
- 该研究重点研究了与RNA模板产物和两个nsp13螺旋酶分子复合的SARS-CoV-2 holo-RdRp (nsp7/nsp82/nsp12).
- 结构分析确定了特定的分子接触点和结合点.
主要成果:
- 这些结构显示了nsp13螺旋酶N终端域与nsp8 N终端扩展之间的相互作用,以及一个nsp13与nsp12指之间的接触.
- nsp13酶的ATPase域的定位表明其在复制中的作用受到功能限制.
- 在nsp12 N-终端域中发现了一种含有ADP-Mg2+的新型结合囊.
结论:
- 这些结构数据为SARS-CoV-2复制机制提供了详细的分子理解.
- 鉴定到的相互作用和结合部位为nsp13酶的功能提供了新的见解.
- 新发现的nsp12结合口袋代表了针对SARS-CoV-2的新型抗病毒药物的开发的一个有希望的目标.
更多相关视频
08:53Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
742
10:11Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
Published on: July 26, 2024
1.5K
相关概念视频
00:55DNA Helicases
23.5K
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...
23.5K
03:01The Replisome
37.6K
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...
37.6K
03:01The Replisome
9.1K
9.1K
02:38S-Cdk Initiates DNA Replication
5.2K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
5.2K
01:02The DNA Replication Fork
39.8K
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...
39.8K
01:02The DNA Replication Fork
17.6K
17.6K