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双重重复的人类端粒d ((TAGGGTTAGGGT) 序列形成了溶液中并行和反并行G四重复的相互转换:不同的拓,热力学特性和折叠/展开动力学
Anh Tuân Phan1, Dinshaw J Patel
1Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. phantuan@sbmr1.mskcc.org
Journal of the American Chemical Society
|December 5, 2003
概括
人类端粒DNA序列可以形成平行和反平行G-四重复结构. 序列的修改会影响这些G-四重复的稳定性和折叠动态.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物物理学 分子生物物理学
背景情况:
- G四复合体是核酸二次结构,在富含关氨酸的序列中形成.
- 已知人类端粒序列形成G-四重复合体,它们在端粒稳定性中起作用.
- 了解G四复合体的结构多样性和动态对于它们的生物学影响至关重要.
研究的目的:
- 为了研究平行和反平行G-四重复的形成和结构特征,从一个两重复的人类端粒序列.
- 检查特定基因修改对G-四重复结构和稳定性的影响.
- 探索不同G-四重复合适体的相互转换和温度依赖的折叠动态.
主要方法:
- 核磁共振 (NMR) 光谱法被用来确定溶液中的G四重复的结构.
- 进行了修改的端粒DNA序列的化学合成.
- 对NMR数据的分析提供了对平行/反平行方向,循环结构和基糖体构造的洞察.
主要成果:
- 没有修改的人类端粒序列d ((TAGGGTTAGGGT) 形成了平行和反平行二维G四重复.
- 一个带有 uracil 置换的序列 (d(TAGGGUTAGGGT)) 主要形成具有双链反转环的平行二维 G-四重复.
- 一个带有替代的序列 (d(UAGGGT(Br) UAGGGT)) 主要形成一个带有边缘环的反平行二维G-四重复.
- 两个G-四重复结构被证明是共存和相互转换的.
- 温度依赖的研究揭示了平行和反平行形式的明显折叠和展开动力学.
结论:
- 人类端粒序列d ((TAGGGTTAGGGT) 呈现结构多态,形成平行和反平行二维G四重复.
- 基调的修改可以选择性地稳定平行或反平行G-quadruplex结构.
- 这些G-四重复形式的相互转换和差异性温度依赖的稳定性突出显示了它们在溶液中的动态性质.
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