ブラキューリ転写因子のTドメイン-DNA複合体の結晶構造
1European Molecular Biology Laboratory, Grenoble Outstation, France. mueller@embl-grenoble.fr
Nature
|February 12, 1998
まとめ
胚の発達に不可欠なTボックス遺伝子ファミリーが,DNA結合ドメイン構造を明らかにした. このXenopus laevis TドメインはDNAをダイマーとして結合し,新しいDNA認識メカニズムを発見します.
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
- 遺伝学 遺伝学とは
背景:
- ブラキューリ (T) 遺伝子は,T-ボックス遺伝子ファミリーの重要なメンバーで,胚の発達に不可欠な転写レギュレータをコーディングしています.
- T-box遺伝子は,脊椎動物と無脊椎動物の間で保存され,突然変異は重度の胚性欠陥につながり,組織の特異化とオルガノゲネシスにおけるその役割を強調します.
- Tボックスには,約180個のアミノ酸からなる保存されたDNA結合ドメイン (Tドメイン) がコード化されています.
研究 の 目的:
- DNAと複合したXenopus laevisのTドメインの3次元構造を解明する.
- Tボックスタンパク質とDNAの相互作用の基礎にある分子メカニズムを理解する.
主な方法:
- X線結晶学を用いて,24ヌクレオチドパリンドロミックDNAデュプレックスに結合したXenopus laevis Tドメインの構造を決定した.
- 構造分析は,タンパク質-DNAインターフェースとDNA認識の方法に焦点を当てました.
主要な成果:
- TドメインはDNAにダイマーとして結合し,メジャーとマイナーの両方の溝と相互作用します.
- 新しいDNA認識モードが特定され,カーボキシ-ターミナルヘリックスがDNAの曲げを誘導することなく,拡大された小溝に深く挿入されました.
- マイナー・グリューブのシーケンス固有の認識は,水害性相互作用とグアニンとのユニークなメインチェーンカルボニル接触によって媒介されます.
結論:
- 決定された構造は,タンパク質-DNA認識のための新しいメカニズムを明らかにし,特にTドメインとDNAマイナー・グリューブの相互作用を強調しています.
- この発見は,Tボックスタンパク質による転写調節と,発達過程におけるそれらの重要な役割についての理解を広げています.
関連する概念動画
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Eukaryotic Transcription Activators
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Single-Strand DNA Binding Proteins
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...


