在连续的GGAADNA位点上形成FLI1丝的结构和合作形成
Caixia Hou1, Oleg V Tsodikov1,2
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States.
Nucleic acids research
|March 25, 2025
概括
研究人员发现了Ewing肉瘤中的FLI1蛋白如何结合DNA. 这种合作结合形成了一个线索,为癌症的发展和潜在的药物点提供了新的见解.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 尤文肉瘤是一种由EWS-FLI1融合蛋白驱动的儿科癌症.
- FLI1的DNA结合域 (DBD) 对于瘤发生至关重要.
- EWS-FLI1与GGAA微卫星结合,但该机制尚不清楚.
研究的目的:
- 阐明FLI1 DBD与相连的GGAA位点结合的机制.
- 了解通过FLI1.1对合作性DNA结合的结构基础.
主要方法:
- 使用X射线晶体学来确定FLI1 DBD-DNA复合物的结构.
- 具有不同数量的GGAA重复的寡合体与FLI1 DBD蛋白质复合.
主要成果:
- FLI1 DBD 与相邻的 GGAA 站点进行合作绑定.
- 通过晶体学揭示了一个核蛋白丝结构.
- 这些结构解释了合作结合和丝形成的基础.
结论:
- 获得了对 EWS-FLI1 致癌功能的机械洞察力.
- 了解FLI1 DNA结合是针对EWS-FLI1.1的里程碑.
相关概念视频
Formation of Higher-order Actin Filaments
2.9K
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
The high-order actin...
2.9K
Generation of Straight or Branched Actin Filaments
2.8K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
2.8K
Formation of Intermediate Filaments
2.9K
Intermediate filaments are cytoskeletal proteins with higher tensile strength and flexibility than microfilaments and microtubules. Unlike the other two cytoskeletal proteins, intermediate filament formation lacks the enzymatic activity to hydrolyze nucleotides like ATP and GTP to generate energy for polymerization. Therefore, the formation of intermediate filaments is multistep self-assembly. The involvement of any accessory proteins in intermediate filament formation has not yet been...
2.9K
Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
Actin Polymerization
6.2K
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight...
6.2K
Actin Filament Depolymerization
3.0K
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
3.0K


