The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B^act spliceosome at 3.4 Å resolution. In the B^act state, the spliceosome is activated but not catalytically primed, so that it is functionally blocked prior to the first catalytic step of splicing. The spliceosomal core is similar to the yeast B^act spliceosome; important differences include the presence of the RNA helicase aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior of the purified spliceosome, we developed a principal component analysis-based approach. Calculating the energy landscape revealed eight major conformational states, which we refined to higher resolution. Conformational differences of the highly flexible structural components between these eight states reveal how spliceosomal components contribute to the assembly of the spliceosome, allowing it to generate a dynamic interaction network required for its subsequent catalytic activation.

中文翻译：

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人剪接细菌复合体的结构和构象动力学。

剪接体是一种高度动态的大分子复合物，可精确地从前mRNA中切除内含子。在这里，我们报告了人类B^行为剪接体在3.4分辨率下的cryo-EM 3D结构。在B^作用状态下，剪接体被激活但未催化引发，因此在剪接的第一个催化步骤之前，其功能被封闭。剪接体核心类似于酵母B的^行为剪接体 重要的区别包括存在RNA解旋酶水瓶座和肽基脯氨酰异构酶。为了检查纯化的剪接体的整体动态行为，我们开发了一种基于主成分分析的方法。计算能量分布图揭示了八个主要构象状态，我们对其进行了精炼以提高分辨率。这八个状态之间的高柔性结构组分的构象差异揭示了剪接体组分如何促进剪接体的组装，从而使其产生随后的催化活化所需的动态相互作用网络。