在人类血小板衍生的生长因子受体β促进体中形成的主要G-四重复合体在K+溶液中采用了新的断链结构
Yuwei Chen1, Prashansa Agrawal, Robert V Brown
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 East Mabel Street, Tucson, Arizona 85721, USA.
Journal of the American Chemical Society
|August 8, 2012
概括
研究人员在血小板衍生生生长因子受体β (PDGFR-β) 基因促进器中发现了一种新的DNA G-四重复结构. 这种独特的结构,带有断裂的G链,为开发治疗PDGFR-β相关癌症和纤维性疾病的药物提供了新的目标.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 血小板衍生生长因子受体β (PDGFR-β) 的过度表达与癌症和纤维性疾病有关.
- 对于这些疾病,PDGFR-β是治疗点.
- 在PDGFR-β促进体中的DNAG四重复体抑制了其转录.
研究的目的:
- 为了确定人类PDGFR-β基因促进体中主要的G-四重复结构.
- 了解这个G-四重复的结构特征.
- 为了探索其作为毒品目标的潜力.
主要方法:
- 对DNAG-四重复的结构分析.
- 对促进子G-四重复折叠的研究.
- 对G-四重复图案的生物信息分析.
主要成果:
- 在PDGFR-β促进体中发现了一种新的G-四重复结构.
- 这种G-四重复体具有断裂的G-链和主要平行链的分子内折叠.
- 它包含三个1核酸 (nt) 双链反转环和一个侧环.
- 该结构突出显示了具有1nt循环的平行G-四重复的稳定性.
结论:
- 新型PDGFR-β促进体G-四重复结构是小分子药物的潜在目标.
- 针对这种结构可以调节PDGFR-β基因表达以获得治疗效益.
- 1-nt循环的G{i) NG{j) 图案可能是促进子G-四复合体中进化选择的结构元素.
相关概念视频
02:37Restarting Stalled Replication Forks
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, a...
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:18Structure and Function of Platelets
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...