在大肠杆菌中突变的远程破坏稳定的影响 β Clamp Dimer 接口
Melissa L Liriano1, Madison B Berger2, Kenny Nguyen1
1Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Biochemistry
|June 27, 2025
概括
细菌β的滑动.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- β滑动是DNA聚合酶III的关键细菌过程性因素.
- 它将聚合酶与DNA结合在一起,提高复制效率和过程性.
- 紧固件加载涉及一个多子单元复合体将二维β紧固件加载到DNA上.
研究的目的:
- 为了研究特定残留物 (Q265,R269) 在β紧管二元接口稳定性和功能的作用.
- 为了确定这些残留物的突变是否可以挽救不稳定的L82Dβ变体的活性.
- 阐明非共价相互作用对β二聚体稳定性的贡献.
主要方法:
- 在野生类型和L82D背景中的β结残留物 (Q265,R269) 的位点定向突变发生.
- 测试以评估的热稳定性,二元化状态和DNA加载活动.
- 分子建模用于分析结构变化和相互作用网络.
主要成果:
- R269残留物对于维持β二聚体稳定性,寡聚体状态和DNA加载至关重要.
- 突变Q265A被容忍,这表明Q265对这些功能不必不可少.
- 在L82D变体中破坏R269相互作用,形成替代网络,与稳定性和活性降低相关.
结论:
- 非对应相互作用的微妙平衡决定了β滑动接口的稳定性.
- 特定的残留物,特别是R269,在维护的完整性和功能方面发挥着至关重要的作用.
- 了解这些相互作用可以了解DNA复制机制和潜在的治疗点.
相关概念视频
Mismatch Repair
5.2K
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...
5.2K
Genome Copying Errors
4.4K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.4K
Mutations in Microorganisms
91
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
91
Translesion DNA Polymerases
10.2K
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...
10.2K
Restarting Stalled Replication Forks
5.9K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.9K
Microtubule Instability
5.3K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.3K


