线粒体单链DNA结合蛋白与DNA和DNA聚合酶 γ 的结构
Amanda A Riccio1, Jonathan Bouvette2, Lars C Pedersen3
1Mitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Nucleic acids research
|August 6, 2024
概括
线粒体单链DNA结合蛋白 (mtSSB) 与DNA的相互作用及其在复制中的作用在结构上得到了阐明. 这为导致线粒体疾病的突变提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 遗传学 是一个
背景情况:
- 线粒体单链DNA结合蛋白 (mtSSB/SSBP1) 对于维护线粒体DNA (mtDNA) 完整性至关重要.
- 在SSBP1的临床突变与严重的线粒体疾病有关.
- 人们对mtSSB-ssDNA相互作用的分子机制及其与其他复制因子的相互作用的了解很少.
研究的目的:
- 阐明mtSSB与单链DNA (ssDNA) 结合的结构基础.
- 研究mtSSB和线粒体DNA聚合酶 (Polγ) 之间的相互作用.
- 为SSBP1相关的线粒体疾病提供结构性见解.
主要方法:
- 通过X射线晶体学,以1.9-Å分辨率确定人体mtSSB与ssDNA结合的结构.
- 位点定向突变发生,以确认DNA结合位点.
- 电子显微镜 (cryo-EM) 用于分析四重体组件和与Polγ的相互作用.
主要成果:
- 高分辨率的晶体结构揭示了 mtSSB 上两个不同的 ssDNA 结合位点:一个低亲和度位点和一个高亲和度位点.
- 高亲和度部位涉及关键残留物R38和W84,对DNA结合和稳定性至关重要.
- 冷EM证实了mtSSB四聚体的形成及其与Polγ.γ的相互作用接口.
结论:
- 该研究揭示了mtSSB与ssDNA的详细分子相互作用,突出了关键残留物和结合方式.
- 对mtSSB-Polγ相互作用的结构洞察力为了解线粒体DNA复制提供了基础.
- 这项工作为与线粒体疾病相关的SSBP1突变提供了分子基础.
更多相关视频
相关概念视频
Single-Strand DNA Binding Proteins
14.0K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.0K
The Replisome
33.3K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
33.3K
DNA Helicases
21.3K
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...
21.3K
Nucleic Acid Structure
6.1K
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...
6.1K
DNA Topoisomerases
31.1K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.1K
Translesion DNA Polymerases
9.9K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
9.9K


