美国斯坦福大学Wah Chiu等研究人员合作解析出3.1Å分辨率的全长四膜虫核酶冷冻电镜结构。2021年8月11日，《自然》杂志在线发表了这项成果。
研究人员报道了全长的四膜虫核酸酶在无底物和结合状态下的冷冻电镜（cryo-EM）结构，分辨率为3.1埃。新解析的外围区域形成了两个同轴堆叠的螺旋；这些螺旋由两个吻环假结点相互连接，环绕着催化核心，包括两个以前未曾预见的三级相互作用。全局结构在两种状态下几乎是相同的；只有内部引导序列和鸟苷结合位点在结合RNA底物时分别发生了较大的构象变化和局部转移。这些结果提供了一个典型RNA酶的结构视图，并标志着基于cryo-EM的核糖核酸酶结构-功能关系研究进入了一个新时代。
据了解，单粒子cryo-EM已经成为在原子分辨率确定蛋白质结构的标准技术。然而，对无蛋白RNA的cryo-EM研究还处于早期阶段。四膜虫第一组自我剪接的内含子是第一个被发现的核酶，并且一直是研究RNA催化和结构-功能关系的一个突出的模型系统，但它的完整结构仍然是未知的。
附：英文原文
Title: Cryo-EM structures of full-length Tetrahymena ribozyme at 3.1 Å resolution
Author: Su, Zhaoming, Zhang, Kaiming, Kappel, Kalli, Li, Shanshan, Palo, Michael Z., Pintilie, Grigore D., Rangan, Ramya, Luo, Bingnan, Wei, Yuquan, Das, Rhiju, Chiu, Wah
Issue&Volume: 2021-08-11
Abstract: Single-particle cryogenic electron microscopy (cryo-EM) has become a standard technique for determining protein structures at atomic resolution1,2,3. However, cryo-EM studies of protein-free RNA are in their early days. The Tetrahymena thermophila group I self-splicing intron was the first ribozyme to be discovered and has been a prominent model system for the study of RNA catalysis and structure–function relationships4, but its full structure remains unknown. Here we report cryo-EM structures of the full-length Tetrahymena ribozyme in substrate-free and bound states at a resolution of 3.1 . Newly resolved peripheral regions form two coaxially stacked helices; these are interconnected by two kissing loop pseudoknots that wrap around the catalytic core and include two previously unforeseen (to our knowledge) tertiary interactions. The global architecture is nearly identical in both states; only the internal guide sequence and guanosine binding site undergo a large conformational change and a localized shift, respectively, upon binding of RNA substrates. These results provide a long-sought structural view of a paradigmatic RNA enzyme and signal a new era for the cryo-EM-based study of structure–function relationships in ribozymes.
DOI: 10.1038/s41586-021-03803-w
Source: https://www.nature.com/articles/s41586-021-03803-w
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
