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对RNA四重复的连接体相互作用的结构描述,从伪狂犬病病毒的非编码区域折叠出RNA四重复

Yashu Zhang¹, Khair Bux², Fedaa Attana³

¹Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, WC1N 1AX, UK; Key Laboratory of Pesticide Toxicology and Application Technique, College of Plant Protection, Shandong Agricultural University, Taian, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.

|June 14, 2024

概括

纳弗他林二胺ND11与来自伪病毒 (PRV) 的特定RNA G-四重复结构结合. 这种相互作用稳定了RNA G-四重复,配体结构影响结合和稳定性.

科学领域:

结构生物学结构生物学
在RNA生物学,RNA生物学.
药用化学医学化学

背景情况:

RNA G-四复合体是关键的核酸结构,参与各种生物过程.
特定的配体可以针对治疗目的的RNA G-四重复合体.
伪病毒 (PRV) 的非编码区域含有假定的RNA G-四重复形成序列.

研究的目的:

为了阐明纳夫他林二胺 (NDI) 连接物与PRV基因组中的RNA G-四重复的结合机制.
为了确定连体-RNA G-四重复相互作用的结构基础.
评估NDI配体对RNA G-四重复结构的稳定作用.

主要方法:

使用X射线晶体学来确定ND11-RNA G-四重复合物的结构.
循环二元化 (CD) 光谱法被用于分析连接体-RNA相互作用.
进行了Förster共振能量转移 (FRET) 融试验,以评估RNA G-四重复稳定性.

主要成果:

该rPRVRNA序列形成了一个双分子G-四重复合体,有3'-to-5'叠叠的四位数.
ND11与RNA G-四重复的5'和3'四重复结合.
在CUC循环和终端A14残留物中的结构变化有助于ND11结合.
对CD的分析表明,各种NDI配体具有共同的结合模式.
在FRET化试验中,NDI化合物显著稳定了RNA G-四倍体.

结论:

通过独特的相互作用模式,ND11合理化了特定的连接体与RNA G-四重复合体的结合.
该研究提供了对RNA G-四重复的结构可塑性的洞察力,以应对连接体结合.
替代的NDI化合物是PRVRNA G-四重复的有效稳定剂,替代剂的长度影响热稳定性.

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