ガイドストランドを含むアルゴナウト静音化複合体の構造
Yanli Wang1, Gang Sheng, Stefan Juranek
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nature
|August 30, 2008
まとめ
RNA誘発サイレンシング複合体は,RNA誘発サイレンシング複合体である.
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- バイオケミストリー バイオケミストリー
背景:
- RNA誘発サイレンシング複合体 (RISC) は,遺伝子調節において極めて重要です.
- RISC内のアルゴナウトタンパク質はスライサー活性を持ち,シーケンス固有のmRNA分裂を可能にします.
- アルゴナウトの構造を理解することは,そのメカニズムを解読する鍵です.
研究 の 目的:
- DNAガイドストランドに結合したThermus thermophilus Argonauteの結晶構造を決定するために.
- ガイドストランド結合とターゲット認識に関与する構造的特徴と形状の変化を特定する.
- アルゴナウトの触媒活性における特定のドメインと残留物の役割を解明する.
主な方法:
- 5'-リン酸化DNA誘導鎖を複合したThermus thermophilus ArgonauteのX線結晶学.
- 分裂活動に対する突然変異の影響を評価するための生化学的測定法.
主要な成果:
- 結晶構造は,PAZとPIWIドメインの間の核酸結合チャネルを示しています.
- DNAガイドストランドは両端に固定され,標的mRNA核形成のためのベース2-6が配置されています.
- 特定のアルギニンは,分裂部位における塩基10−11の正交的調整を誘導する.
- 主要な活性部位の残留物と5'-ホスファート結合ポケットは,分裂に不可欠である;PAZドメインの3'-エンド結合ポケットは,最小限の影響を及ぼします.
結論:
- この構造は,アルゴナウトのガイド・ストランド・バインディングとターゲット認識メカニズムに関する洞察を提供します.
- 特定の残留物とドメイン相互作用は,アルゴナウトのPIWIドメインの触媒活性に不可欠です.
- この研究は,RNAの干渉の分子基礎についての私たちの理解を前進させます.
関連する概念動画
01:23RNA 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...
02:26Conservation 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...
01:23RNA 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...
02:30siRNA - 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...
02:57piRNA - 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...
02:15Experimental 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...