核酸触发的短细胞阿尔戈诺亚的NADase激活
Xiaopan Gao1,2, Kun Shang3,4, Kaixiang Zhu1,2
1NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nature
|October 2, 2023
概括
这项研究揭示了短细胞阿尔戈诺特 (pAgo) 蛋白质的结构,揭示了它们防御入侵核酸的机制. 这些发现揭示了SPARTA复合体的功能,并为DNA检测应用提供了洞察力.
科学领域:
- 结构生物学
- 分子生物学
- 生物化学
背景情况:
- 在核酸引导的抑制中,阿戈蛋白质至关重要.
- 已知真核和长 prokaryotic Ago 蛋白的机制,但短 pAgos 的机制尚不清楚.
- 短的pAgos参与了对外来核酸的防御.
研究的目的:
- 确定 Crenotalea thermophila 的一个短 pAgo-TIR-APAZ 复合体 (SPARTA) 的冷电子显微镜结构.
- 阐明短时间pAgo介导核酸抑制的结构基础.
- 为开发基于SPARTA的可编程DNA检测系统提供见解.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定Crt-SPARTA在各种状态中的结构 (自由,RNA-DNA结合,二聚体,四聚体).
- 突变性研究以支持功能性见解.
- 蛋白质核酸相互作用和复杂组合的结构分析.
主要成果:
- 确定了自由,RNA-DNA结合,二元和四元Crt-SPARTA的结构.
- 显示Crt-SPARTA包括一个双球Ago叶和一个TIR叶,具有不同的域.
- 在核酸结合时发现的构造变化,包括触发域路障和MID域障碍,促进二元化.
- 显示两个二聚体通过TIR域形成四聚体,采用NADase活性构造.
结论:
- 这项研究揭示了短时间抗核酸防御的结构基础.
- 核酸结合带来的形状变化是SPARTA功能的关键.
- 这些发现为优化基于SPARTA的可编程DNA检测提供了潜力.
更多相关视频
相关概念视频
Conservation of Protein Domains Over Different Proteins
10.9K
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...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.9K
siRNA - Small Interfering RNAs
16.8K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.8K
RNA Interference
26.1K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.1K
Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
Nucleic Acid Structure
6.2K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
6.2K
Ribozymes
12.3K
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...
Ribozymes can...
12.3K


