美国应用分子进化研究所Benner Steven A.团队报道了由扩展的基因字母表形成的折叠基序。相关研究成果发表在2024年6月10日出版的国际学术期刊《自然—化学》。

在DNA中添加合成核苷酸可以增加DNA分子的线性信息密度。

该文中，研究人员它还可以增加其三维褶皱的多样性。具体来说，一个额外的位于23个核苷酸长的DNA链的12个位点的核苷酸（dZ，带有5-硝基-6-氨基吡啶酮核碱基），产生了一个相当稳定的在66.5°C、pH 8.5下融化的单分子结构（即折叠的Z基序或fZ基序）。光谱、凝胶和二维NMR分析表明，折叠的Z基序由六个反向的瘦dZ:dZ碱基对连接在一起，类似于自由杂环的晶体结构。

荧光标记显示，dZ:dZ对以四股紧密的下-上-下-上折叠的方式连接平行链。它们有两种可能的结构：一种带有嵌入的dZ:dZ碱基对，另一种没有嵌入。插入的结构类似于在pH≤6.5时由dC:dC+反向配对形成的i基序。因此，这种fZ基序可以帮助DNA形成结合和催化所需的紧密结构。

附：英文原文

Title: A folding motif formed with an expanded genetic alphabet

Author: Wang, Bang, Rocca, James R., Hoshika, Shuichi, Chen, Cen, Yang, Zunyi, Esmaeeli, Reza, Wang, Jianguo, Pan, Xiaoshu, Lu, Jianrong, Wang, Kevin K., Cao, Y. Charles, Tan, Weihong, Benner, Steven A.

Issue&Volume: 2024-06-10

Abstract: Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5°C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ:dZ pairs join parallel strands in a four-stranded compact down–up–down–up fold. These have two possible structures: one with intercalated dZ:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH≤6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.

DOI: 10.1038/s41557-024-01552-7

Source: https://www.nature.com/articles/s41557-024-01552-7