核細胞結合DNAメチルトランスファーゼDNMT3AとDNMT3Bの構造
Ting-Hai Xu1,2, Minmin Liu2, X Edward Zhou1
1Center for Cancer and Cell Biology, Program for Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Nature
|September 24, 2020
まとめ
De novo DNAメチルトランスファーゼ (DNMTs) 3Aと3Bは,発育と癌にとって極めて重要です. 核分裂体との相互作用は 凍結-EMによって示され 甲基化のためにDNAにアクセスする方法が示されています
科学分野:
- エピジェネティクス
- 分子生物学
- 構造生物学
背景:
- DNAメチル化は哺乳類の発達と分化に不可欠です
- DNAメチルトランスフェラーゼ (DNMTs) の調節不全は,がんにおいて一般的です.
- DNMT3AとDNMT3Bは核細胞を優先的に結合するが,包んだDNAをメチル化するのに苦労する.
研究 の 目的:
- DNAメチル化の構造的メカニズムを明らかにする.
- DNMT3AとDNMT3BがDNAにアクセスするためにどのように相互作用するのかを理解する.
主な方法:
- クリオ電子顕微鏡 (cryo-EM) を用いて三元複合体の構造を決定した.
- コンプレックスには,触媒的に有能なDNMT3A2,不活性なDNMT3B3と,リンカーDNAを持つ核細胞核粒子が含まれていた.
主要な成果:
- 構造は,DNMT3B3が核細胞の酸性パッチに結合し,DNMT3A2をリンク器DNAに指向することを明らかにした.
- ステリック制約は,メチル化のためにDNAの再定位が必要であることを示しています.
- これは,DNMTがリンクDNAを好む構造的根拠を提供する.
結論:
- この研究では,DNMT3A2とDNMT3B3が核細胞と相互作用する正確なメカニズムが明らかになりました.
- この相互作用は,酵素を正しく配置することで,DNAメチル化を容易にする.
- この過程を理解することは,表遺伝的調節と癌の発達を理解するために非常に重要です.
関連する概念動画
01:12The Nucleosome Core Particle
2.0K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
2.0K
02:10The Nucleosome Core Particle
13.7K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
13.7K
02:54Nucleosome Remodeling
10.4K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.4K
02:25Spreading of Chromatin Modifications
9.1K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.1K
00:55DNA Helicases
23.5K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
23.5K
01:25Nucleic Acid Structure
8.1K
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...
DNA Structure
DNA...
8.1K