相关实验视频

Updated: Jul 14, 2025

Engineering Antiviral Agents via Surface Plasmon Resonance

Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

对SARS-CoV-2 NiRAN域的酶可塑性的结构和功能洞察

Gabriel I Small¹, Olga Fedorova^2,3, Paul Dominic B Olinares⁴

¹Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

bioRxiv : the preprint server for biology

|October 9, 2023

概括

在SARS-CoV-2的NiRAN域.

科学领域:

病毒学病毒学
结构生物学结构生物学
生物化学生化学

背景情况:

SARS-CoV-2 尼多病毒 RdRp 关联核样转移酶 (NiRAN) 域对于病毒复制至关重要.
尼兰表现出三种活动:NMPylation,RNAylation和deRNAylation/capping,后两个形成病毒RNA5'-caps.
这些多样化的酶功能的结构基础在很大程度上仍然未被描述.

研究的目的:

阐明了NiRAN域的酶活性背后的结构机制.
了解核酸结合和金属离子协调在NiRAN功能中的作用.
为开发针对 NiRAN 的治疗提供结构性基础.

主要方法:

高分辨率的冷电子显微镜 (cryo-EM).
确定NMPylation和deRNAylation/capping反应的催化中间体的结构.
分析核酸结合姿势和双价金属离子协调.

主要成果:

获得了NiRAN催化中间体的详细冷-EM结构.
确定了各种核酸结合模式和金属离子协调部位.
该结构解释了GDP在上限反应中对GTP的偏好.

结论:

这项研究揭示了SARS-CoV-2 NiRAN多样化的酶活动的结构机制.
这些发现凸显了NiRAN域的杂乱性及其在病毒传播中的重要性.
这些结构性见解为设计针对这种必不可少的病毒酶的药物提供了基础.

关键词:

通过NMP化进行了NMP化.尼兰域名 (NiRAN) 是一个域名.这是一种RNA基化.这就是SARS-CoV-2病毒.封闭上限是指封闭上限.冠状病毒冠状病毒的新冠病毒.低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.这是一种deRNAylation的过程.在 mRNA 封顶上.

更多相关视频

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Published on: December 9, 2022

Structural Studies of Macromolecules in Solution using Small Angle X-Ray Scattering

Structural Studies of Macromolecules in Solution using Small Angle X-Ray Scattering

Published on: November 5, 2018

相关概念视频

Leaky Scanning

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

Ribozymes

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can...

Structural Protein Function

Structural Protein Function

Conservation of Protein Domains Over Different Proteins

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...

Bacterial RNA Polymerase

Bacterial RNA Polymerase

Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...