氧化G-四重复的动态结构和快速过渡动力学
Jiahao Ji1, Arpit Sharma1, Pravin Pokhrel1
1Department of Chemistry & Biochemistry, Kent State University, Kent, OH, 44242, USA.
Small (Weinheim an der Bergstrasse, Germany)
|April 28, 2024
概括
在DNA中氧化的关氨酸形成G-四重复合体 (GQs),在拥挤的细胞环境中以不同的方式结合联体. 这一发现影响了在氧化应激下对DNA结构的理解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 氧化应激会损害DNA,导致像8-oxoguanine (8-oxoG) 这样的基因变异.
- 8-oxoG可以改变富含G的DNA序列的结构和功能,包括G-四重复 (GQs).
- 细胞环境是分子拥挤,影响DNA结构和相互作用.
研究的目的:
- 在模拟拥挤的细胞环境中研究氧化人类端粒G-四重复合体 (GQs) 的结构稳定性和连接体结合特性.
- 了解分子拥挤和8-oxoguanine修饰如何影响GQ形成与 (Pt(II)) 结合剂的合作性.
主要方法:
- 模仿细胞拥挤使用40%的DMSO或糖糖.
- 野生类型 (WT) 和氧化GQ的稳定性测试.
- 在拥挤的条件下调查Pt(II) 结合剂合作社.
- 单分子机械展开分析GQ结构动力学和折叠动力学.
主要成果:
- 氧化的人类端粒GQ在拥挤条件下表现出与WT GQ相似的稳定性.
- 虽然WT GQs在拥挤中表现出与Pt(II) 结合剂的负合作性,但氧化GQs表现出正合作性.
- 单分子展开显示氧化GQs形成更多样化的,灵活的结构与更快的动力学,使优先的Pt(II) 结合.
结论:
- 在拥挤的环境中,氧化G丰富的结构表现出独特的折叠动态和改变的连接体结合合作性.
- 这些发现增强了对氧化应激下DNA结构和基因调节的理解.
- 为设计与细胞氧化应激相关的氧化DNA结构的向配体提供了洞察力.
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