人間のキノームにおける特異性の決定因子の解明
Pau Creixell1, Antonio Palmeri2, Chad J Miller3
1Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
Cell
|September 22, 2015
まとめ
研究者は,タンパク質キナーゼ基質の特異性を制御する特異性決定因子 (DoS) と呼ばれる重要なアミノ酸残基を特定しました. この発見により 癌のシグナル伝達と 病気のメカニズムの理解が進んでいます
科学分野:
- 分子生物学
- 生物化学
- 癌 の 信号
背景:
- タンパク質キナーゼは 細胞の信号処理に不可欠で 細胞の信号処理に欠陥があることが 癌を引き起こすのです
- キナーゼにおける基質特異性決定因子 (DoS) の理解は,がんのシグナル伝達経路の解読に不可欠である.
- DoSに関する限られた知識は,標的型がん治療法の開発を妨げています.
研究 の 目的:
- タンパク質キナーゼ基板特異性 (DoS) を決定するアミノ酸残基を体系的に特定し,実験的に検証する.
- キナーゼ特異性を支配する構造的および進化的原理を調査する.
- 癌の信号ネットワークを理解するための DoS 識別の可能性を探求する.
主な方法:
- キナーゼドメイン内の特異性 (DoS) の潜在的決定因子の体系的な計算的発見.
- αC1,αC3およびAPE-7の残留を含む特定されたDoSの実験的検証.
- 残留ネットワークの特性と進化的な保存パターンの分析
主要な成果:
- いくつかの新しい DoS が発見され,3つの主要な残留物 (αC1,αC3,APE-7) が実験的に検証された.
- DoSは保存されていない残留物の稀なネットワークを形成し,特異性におけるアロステリーの役割を示唆しています.
- キナーゼ活性と特異性は進化的に分離され,独立した残基群によって制御される.
結論:
- DoSの識別は,タンパク質キナーゼ基板認識のメカニズムに関する重要な洞察を提供します.
- 遠隔の残基間のアロステリック相互作用は,キナーゼの特異性に大きく貢献する.
- DoSを理解することは,がんにおけるシグナルネットワークの役割を明らかにし,新しい治療戦略を開発するために不可欠です.
さらに関連する動画
関連する概念動画
01:57Protein Complexes with Interchangeable Parts
3.1K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.1K
02:30Histone Variants at the Centromere
5.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.3K
02:32Histone Modification
17.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
17.3K
02:04Covalently 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
02:51Multi-species Conserved Sequences
4.9K
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
4.9K
01:49Conserved 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