関連する実験動画
Updated: Apr 13, 2026

16:24
Analyzing and Building Nucleic Acid Structures with 3DNA
Published on: April 26, 2013
21.4K
AML1/Runx-1 RuntドメインによるDNA認識とCBFbetaによるそのアロステリックコントロールの構造分析
T H Tahirov1, T Inoue-Bungo, H Morii
1Kanagawa Academy of Science and Technology (KAST), Yokohama City University School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Kanazawa-ku, Japan. tahir@med.yokohama-cu.ac.jp
Cell
|March 21, 2001
まとめ
核結合因子 (CBF) の転写因子は,細胞の分化に不可欠である. 彼らの構造は,CBFβがDNA結合を調節する方法を明らかにし,白血病や骨発育疾患の洞察を提供します.
科学分野:
- バイオケミストリーと分子生物学
- 構造生物学 構造生物学とは
- 遺伝学 遺伝学とは
背景:
- AML/CBFA/PEBP2alpha/RunxおよびCBFbeta/PEBP2betaサブユニットで構成されるコア結合因子 (CBF) の転写因子は,血液形成および骨細胞の分化に極めて重要です.
- CBFの突然変異は,急性白血病と小頭蓋骨不形成症に関連しており,人間の健康におけるその重要性を強調しています.
研究 の 目的:
- コア・バインディング・ファクター (CBF) 機能の構造的基礎を解明する.
- CBFベータによるCBFアルファ-DNA結合のアロステリック調節メカニズムを理解する.
- CBFalphaの疾患関連の変異をマッピングし,DNA結合への影響を評価する.
主な方法:
- 様々なCBF-DNA複合体の構造を決定するために,X線結晶学を用いた.
- 複合体内の水素結合ネットワークの分析.
- 特定の疾患に関連する点変異のマッピング.
主要な成果:
- AML1/Runx-1/CBFalpha (ラントドメイン) -CBFbeta (コアドメイン) -C/EBPbeta (bZip) -DNA,AML1/Runx-1/CBFalpha (ラントドメイン) -C/EBPbeta (bZip) -DNA,およびAML1/Runx-1/CBFalpha (ラントドメイン) -DNA複合体の結晶構造が得られました.
- 詳細な水素結合ネットワークは,CBFbeta.によってCBFalpha-DNA結合のアロステリック調節を明らかにした.
- CBFalphaの病気に関連した点変異がマッピングされ,DNA結合への影響が分析されました.
結論:
- 結晶構造は,CBF媒介による遺伝子調節のメカニズム的理解を提供します.
- CBFββはCBFalpha.のDNA結合親和性をアロステリックに調節する.
- これらの構造的および規制的メカニズムを理解することは,CBFに関連する疾患に対する治療戦略の開発に不可欠です.
関連する概念動画
Conserved Binding Sites
5.3K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.3K
Covalently Linked Protein Regulators
9.9K
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....
9.9K
Cooperative Binding of Transcription Regulators
7.6K
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...
7.6K
Co-activators and Co-repressors
9.0K
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...
9.0K
Eukaryotic Transcription Activators
13.5K
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...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
13.5K
Allosteric Proteins-ATCase
7.0K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
7.0K

