BG4抗体可以识别带有破坏稳定的基基修饰和病变的端粒G-四重复合体
Samuel A Johnson1,2,3, Tapas Paul4,5, Samantha L Sanford1,2
1Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, PA 15261, USA.
Nucleic acids research
|December 28, 2023
概括
BG4抗体与高 afinity 的端粒 G-四重复合体 (GQs) 结合,即使有 DNA 损伤. 这种抗体可以促进这些重要的G-四重复结构的稳定性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- G四重复体 (GQs) 是四链DNA结构,涉及各种细胞过程.
- 众所周知,具有重复性TTAGGG序列的端粒DNA可以形成GQ.
- BG4抗体是多种GQ拓的高亲和结合剂.
研究的目的:
- 为了研究BG4抗体与端粒G-四重复合体的结合特性.
- 为了确定DNA序列长度,修改和损伤对BG4结合亲和力的影响.
- 探索BG4结合对端粒GQ稳定性的功能影响.
主要方法:
- 与酶相关的免疫吸收试验 (ELISA) 用于结合亲和度测量.
- 单分子拉下 (SiMPull) 试验与福斯特共振能量转移 (FRET) 相结合.
- 原子力显微镜 (AFM) 用于立体测量分析.
主要成果:
- 不管长度如何,BG4对端粒GQs具有高亲和力结合,对不能形成稳定的GQs的结构有较低的亲和力.
- 单个关氨酸替代物降低了BG4亲和力,而双重替代物显著减少或取消了结合.
- 损坏的基 (8-oxoguanine,O6-methylguanine) 减少但没有阻止BG4结合.
- BG4结合被证明可以促进端粒GQs的折叠,具有特定的替代或损伤.
- 原子力显微镜证实了BG4和端粒GQs之间的1:1结合静脉测量.
结论:
- BG4有效地结合端粒G-四重复合体,耐受某些序列变异和DNA损伤.
- 抗体可以识别和稳定部分折叠的端粒GQ结构.
- 这些发现凸显了BG4作为研究和潜在调节端粒GQ功能的工具的潜力.
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