Yap1転写因子局所化のリドックス調節のための構造的基礎
Matthew J Wood1, Gisela Storz, Nico Tjandra
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Nature
|August 20, 2004
まとめ
Yap1転写因子は,酸化ストレス中に遺伝子発現を制御する. その構造は二硫化結合によって変化し,核と細胞質の間の動きを調節する.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 生物は生存のために遺伝子発現を環境の変化に適応しなければなりません.
- Yap1転写因子は,Saccharomyces cerevisiaeにおける酸化ストレス反応の管理に重要な役割を果たしています.
- 活性化されたYap1は核に移動し,最大70の遺伝子に影響を与えます.
研究 の 目的:
- Yap1.1.内のリドックス調節ドメインを識別する.
- このドメインの高解像度ソリューション構造を決定します.
- Yap1のサブセルラー局所化制御のメカニズムを解明する.
主な方法:
- Yap1の溶液構造を決定するための構造生物学技術.
- 酸化還元依存相互作用を調査するための生化学的分析.
- 機能ドメインを調査するためのサイト指向型変異.
主要な成果:
- Yap1における酸化還元調節ドメインが特定され,構造的に特徴づけられました.
- 酸化状態では,Yap1の核輸出信号 (NES) は二硫化物結合によってマスクされています.
- 排水性の相互作用の破壊は,酸化還元調節による局所化変化を防ぐことができた.
- ディスルファイド結合の減少は非構造的形状につながり,NESを露出させ,細胞プラズマの再分配を可能にします.
結論:
- この研究は,酸化還元依存型Yap1局所化の構造的基礎を明らかにしています.
- 逆転性ジスルファイド結合による転写因子調節の新しいメカニズムが提示されています.
関連する概念動画
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Transcription Attenuation in Prokaryotes
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Transcriptional Regulation: Riboswitches
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...


