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扭曲四重复的DNA:在多样化的分子拥挤环境中调节i-motif功能的链动态

Shuntaro Takahashi^1,2, Saptarshi Ghosh¹, Marko Trajkovski³

¹FIBER (Frontier Institute for Biomolecular Engineering Research), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.

Nucleic acids research

|June 30, 2025

概括

分子拥挤会影响DNAi-motif的稳定性和功能. 具有六个或更多单位的特定聚乙烯糖醇 (PEG) 和乙烯糖醇 (OEG) 稳定了i-动机DNA,影响了基因调节.

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:

间隙动机 (i-动机) 四重复的DNA对于基因表达和疾病至关重要.
由于很少有已识别的结合蛋白,对细胞内i-motif调节的知识有限.
细胞分子环境被假设是i-motif形成和功能的关键调节者.

研究的目的:

研究多样化的分子拥挤环境如何影响i-motif DNA的稳定性和功能.
阐明分子环境对i-motif调节的化学机制.

主要方法:

使用各种聚乙烯糖醇 (PEG) 和橄乙烯糖醇 (OEG) 来模拟细胞拥挤的系统研究.
通过核磁共振 (NMR) 和分子动力学模拟进行定量验证.
评估低色度变化和溶液特性.

主要成果:

具有六个或更多乙烯基醇单位的PEG和OEG显著稳定了人类端粒i-motif.
较短的PEG/OEG (少于6个单位) 破坏了i-motif的稳定.
由Cosolute诱导的扭曲动力学改变了复制激活能量屏障的两倍大小.

结论:

分子环境,特别是像PEG和OEG这样的拥挤剂,在调节i-motif DNA稳定性和功能方面发挥着重要作用.
聚合剂中的乙烯基醇单元的长度决定了i-motif结构的稳定或不稳定.
这些发现表明,通过分子环境介导的细胞阶段对i-motif生物作用的潜在调节机制.

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