含有指导链的阿尔戈诺特静音复合物的结构
Yanli Wang1, Gang Sheng, Stefan Juranek
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nature
|August 30, 2008
概括
这是一种RNA诱导的沉默复合体.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- RNA诱导的沉默复合体 (RISC) 对于基因调节至关重要.
- 在RISC中的阿尔戈诺特蛋白质具有切片活性,使序列特定的mRNA分裂成为可能.
- 了解阿尔戈诺特的结构是破译其机制的关键.
研究的目的:
- 为了确定与DNA指导链结合的Thermus thermophilus Argonaute的晶体结构.
- 识别指导链结合和目标识别所涉及的结构特征和形状变化.
- 阐明特定域和残留物在阿尔戈诺特的催化活性中的作用.
主要方法:
- 用5'-酸化DNA导向链复合的Thermus thermophilus Argonaute的X射线晶体学.
- 生物化学测试,以评估突变对分裂活动的影响.
主要成果:
- 晶体结构显示了PAZ和PIWI域之间的核酸结合通道.
- 导向DNA链在两端定,基数2-6为目标mRNA核定位.
- 特定的阿基尼因诱导了分裂部位的基数10-11的直角对齐.
- 关键活性位点残留物和5'-酸盐结合口袋对于裂变至关重要;PAZ域的3'-终结结合口袋的影响最小.
结论:
- 该结构提供了关于阿尔戈纳特的指导链结合和目标识别机制的见解.
- 特定的残留物和域相互作用对于Argonaute的PIWI域的催化活性至关重要.
- 这项研究提高了我们对RNA干扰分子基础的理解.
相关概念视频
RNA Interference
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...
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 form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
RNA Interference
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...
siRNA - Small Interfering RNAs
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 ATP-dependent...
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 ATP-dependent...
piRNA - Piwi-interacting RNAs
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
Experimental RNAi
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...


