ガイドRNAを持つ酵母アルゴナウトの構造
Kotaro Nakanishi1, David E Weinberg, David P Bartel
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nature
|June 23, 2012
まとめ
Kluyveromyces polysporus Argonaute (KpAGO) の結晶構造は,ガイドRNAがどのように負荷され,位置づけられているかを明らかにしています. この構造は,RNAの干渉に不可欠なアルゴナウト媒介のRNA分裂のメカニズムを明らかにします.
科学分野:
- バイオケミストリー バイオケミストリー
- 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
背景:
- RNA誘発サイレンシング複合体 (RISC) は,RNA干渉 (RNAi) の中心にある.
- アルゴナウトタンパク質はRISCの重要な構成要素であり,誘導RNAを結合させ,標的の認識と分裂を媒介する.
- アルゴナウトの構造と機能を理解することは,遺伝子調節を解読し,RNAiベースの治療法を開発するために不可欠です.
研究 の 目的:
- ガイドRNAで複合したKluyveromyces polysporus Argonaute (KpAGO) の結晶構造を決定する.
- アルゴナウト内でガイドRNAの負荷と位置づけの構造的基礎を解明する.
- RNAの分裂におけるアルゴナウトの触媒活性に起因する構造的特徴を特定する.
主な方法:
- KpAGO-ガイドRNA複合体の3.2 Å構造を得るためのX線結晶学.
- 特定の残留物や構造要素の役割を調査するために,サイト・ディレクテッド・ミュータジェネシス.
- アルゴナウトの活動を評価するために,RNAの分裂アッセイを含む生化学的アッセイ.
主要な成果:
- 結晶構造は,再結合KpAGOによるガイドRNAの自律的な負荷を明らかにした.
- ガイドRNAヌクレオチド1〜8は,配列に関係なく,保存された,A型に近い形状を採用します.
- KpAGOは,Nドメインを再配置するユニークな挿入セグメントを有し,ガイド-ターゲットペアリングを容易にします.
- 安定したループを介して挿入された保存されたグルタミン酸残基は,触媒ポケットの一部を形成し,保存された触媒テトラドを完了します.
結論:
- KpAGOの構造は,ガイドRNAの結合と定位に関する前例のない洞察を提供します.
- 挿入セグメントとグルタミン酸指を含むKpAGOの構造的適応は,RNA分裂の活性化に不可欠です.
- この研究は,アルゴナウト媒介RNA干渉のメカニズムを明らかにし,関連する生物学的プロセスを理解するための基礎を提供します.
関連する概念動画
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 Structure
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
RNA Structure
Overview
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA): messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three RNA types consist of a...
Nucleic Acid Structure
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 has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...
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...

