冠状病毒双膜囊孔综合体的分子结构
Yixin Huang1, Tongyun Wang2, Lijie Zhong1
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Nature
|August 14, 2024
概括
冠状病毒产生双膜囊泡 (DMV) 进行复制. 研究人员发现了SARS-CoV-2 nsp3-nsp4毛孔复合体的结构,揭示了它在RNA传输和潜在的抗病毒点中的作用.
科学领域:
- 病毒学
- 结构生物学
- 分子生物学
背景情况:
- 冠状病毒重塑宿主细胞膜,形成用于病毒RNA合成的双膜囊泡 (DMV).
- SARS-CoV-2 的非结构性蛋白 nsp3 和 nsp4 对于诱导 DMV 形成和创建 RNA 输送孔隙至关重要.
研究的目的:
- 阐明SARS-CoV-2 nsp3-nsp4毛孔复合体的分子结构.
- 了解DMV毛孔形成的机制及其在病毒RNA转移中的作用.
主要方法:
- 使用冷电子断层扫描 (cryo-ET) 来可视化毛孔复合体.
- 应用了分离的DMV的高分辨率结构.
主要成果:
- nsp3-nsp4孔综合体由nsp3和nsp4的12个副本组成,分别排列成四个同心六合环.
- 跨位膜域诱导膜曲,将孔隙形成与双膜重组相结合.
- 广泛的ectodomain接触和中心正电荷的阿尔金因环表明在RNA转位中发挥作用.
结论:
- 这项研究揭示了SARS-CoV-2 nsp3-nsp4毛孔复合体的详细结构,类似于微型核毛孔复合体.
- 这种结构理解为研究DMV形成和RNA转移提供了框架.
- 这些发现为开发新型抗病毒策略提供了结构性基础.
相关概念视频
Pinching-off of Coated Vesicles
3.1K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Viral Structure
62.0K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
62.0K
COP Coated Vesicles
7.7K
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
7.7K
Multi-pass Transmembrane Proteins and β-barrels
5.2K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
5.2K
Clathrin Coated Vesicles
6.9K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
6.9K
Mechanisms of Membrane Domain Formation
3.0K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.0K


