通过真核DNA识别基质的机制 N6 - 氨酸甲基转移酶复合体
Qi Xu1,2,3, Ying Xie2,3, Zhubing Shi4,5
1School of Life Sciences, Fudan University, Shanghai, China.
Nature communications
|September 30, 2025
概括
细胞DNAN6-甲基亚丁 (6mA) 甲基转移酶 (MTases) 对细胞功能至关重要. 这项研究揭示了与DNA结合的MTA1复合物的结构,阐明了基质识别机制.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 结构生物学 结构生物学
背景情况:
- DNA N6 - 甲基亚丁 (6mA) 修饰对于真核细胞细胞功能至关重要,包括基因调节和DNA修复.
- 精确的机制,即真核DNA6mA甲基转移酶 (MTases) 识别它们的基质仍然在很大程度上未被阐明.
研究的目的:
- 为了确定真核DNA 6mA MTase基质识别的结构基础.
- 阐明由MTA1复合体 (MTA1c) 改变DNA6mA的分子机制.
主要方法:
- 电子显微镜 (Cryo-EM) 用于确定MTA1c-DNA复合体的结构.
- 生物化学试验用于研究基质结合和酶激活.
主要成果:
- 由MTA1,MTA9/9-B,p1和p2子单元组成的MTA1c复合体,将DNA与其表面结合在一起.
- p1亚单元的N端区域紧DNA,并且将目标脱氧腺素翻转出来进行修改.
- 观察到与MTA1c结合的非甲基化和半甲基化DNA基质的不同构造动态.
结论:
- 结构和生化数据为MTA1c.的激活和基质识别提供了洞察力.
- 这项研究为了解真核生物中DNA 6mA修饰的分子机制提供了一个框架.
更多相关视频
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
3.0K
07:16Author Spotlight: Advancements in DNA Nanosensors – Addressing Sensitivity and Selectivity Challenges in Molecular Detection
Published on: February 9, 2024
1.5K
相关概念视频
Mismatch Repair
6.3K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.3K
Mismatch Repair
43.5K
Overview
43.5K
Transfer RNA Synthesis
13.2K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
13.2K
Proofreading
60.0K
Overview
60.0K
Proofreading
8.7K
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase...
Errors During Replication are Corrected by the DNA Polymerase...
8.7K
Allosteric Proteins-ATCase
6.5K
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...
6.5K
