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扩展的遗传字母增加了六个字母DNA的结构和化学多样性,用于高亲和度蛋白质向的受体

Kazuhiro Sawada¹, Michiko Kimoto^2,3, Ken-Ichiro Matsunaga^2,3

¹Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.

Nature communications

|December 16, 2025

概括

不自然的基对在DNA的体中产生高度特定的登革热生物标志物. 低温EM结构揭示了这些新型DNA结构如何实现对登革热非结构蛋白1 (NS1) 的特殊亲和力和特异性.

科学领域:

合成生物学合成生物学
生物化学生物化学
结构生物学是结构生物学.

背景情况:

将遗传字母扩展到不自然的基对 (UBPs) 创造了新的生物聚合物.
像DS-Px/Pa'这样的疏水性UBP能够实现高保真性PCR,用于设计含UB的DNA体 (XenoAptamers).
针对登革热NS1的XenoAptamers具有很高的亲和力和特异性,可以区分微妙的NS1变体.

研究的目的:

阐明XenoAptamer对登革热的特异性和亲和性的分子基础NS1.
确定 UB 含有的 DNA 体增强性质的基础结构机制.

主要方法:

电子显微镜 (cryo-EM) 用于确定NS1-XenoAptamer复合物的结构.
分析有助于体蛋白相互作用的结构特征.

主要成果:

每个XenoAptamer都采用了一种独特,稳定的三级结构,精确地补充了NS1表面.
NS1-XenoAptamer复合物的刚性对于高亲和力和特异性至关重要.
疏水的Ds基因通过堆叠相互作用促进了独特的结构图案.
在NS1上,Pa'的propynyl组被插入到NS1上的疏水口袋中.

结论:

不自然的基对扩大了DNA的结构和物理化学多样性.
UBP能够创建新的核酸模式,在诊断和治疗方面具有潜力.
这些结构洞察力为设计先进的XenoAptamers提供了基础.

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