通过与c-KIT1 G-四倍复合体结合,PARP2的催化活动被全局刺激
Dagur Singh Hanuman1, Singh Neeharika1, Eerappa Rajakumara1
1Macromolecular Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Hyderabad, Telangana 502284, India.
ACS omega
|March 10, 2025
概括
聚 ((ADP-ribose) 聚合酶2 (PARP2) 结合并被G-四重复的DNA结构激活,特别是c-KIT1-G4. 这种结合和激活是全性,揭示了PARP2在基因组稳定中的新调节机制.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 聚ADP-ribose) 聚合酶2 (PARP2) 通过修复DNA断裂来维持基因组稳定性至关重要.
- 通过单链 (SSB) 和双链 (DSB) DNA 断裂刺激PARP2的催化活性.
- 通过G-四重复基DNA结构调节PARP2,这种结构存在于原瘤基因和端粒中,仍未得到研究.
研究的目的:
- 为了研究PARP2和G-四重复DNA结构之间的相互作用.
- 为了确定G-四重复DNA是否可以调节PARP2催化活性.
- 为了阐明PARP2的特定区域参与G-四倍体结合和激活.
主要方法:
- 生物化学试验用于研究PARP2与c-KIT1-G4.4的结合.
- 酶活性测定用于测量PARP2催化活性刺激.
- 位点定向突变发生,以分析PARP2域在DNA结合和活性中的作用.
主要成果:
- PARP2选择性地与原型瘤基因特异的平行G-四重复,c-KIT1-G4.4结合.
- c-KIT1-G4刺激了PARP2的催化活性,虽然比SSBDNA的作用程度要小.
- PARP2的N终端区域和WGR域对于c-KIT1-G4结合很重要,而N终端区域对于催化活性是不可用的.
结论:
- PARP2 具有选择性结合到高阶DNA结构,如G-四复合体.
- G-四重复基因DNA结合会诱导PARP2的全性激活.
- 这项研究揭示了PARP2涉及G-四重复DNA的新型调节途径,影响基因组稳定性维护.
相关概念视频
01:08Allosteric Regulation
57.4K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
57.4K
01:19Allosteric Proteins-ATCase
5.6K
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...
5.6K
00:49Ligand Binding and Linkage
4.7K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.7K
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
02:37DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
01:25cAMP-dependent Protein Kinase Pathways
6.1K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.1K