小柯机器人

瑞典斯德哥尔摩大学Alexey Amunts和瑞典卡罗林斯卡学院Joanna Rorbach共同合作近期取得重要工作进展，他们研究发现了线粒体核糖体小亚基的生物发生和预启动机制。该项研究成果发表在2022年6月8日在线出版于《自然》杂志上。

在这里，研究人员使用低温电子显微镜来确定一系列与辅助因子复合的小线粒体亚基（SSU）中间体，揭示了顺序组装机制。甲基转移酶TFB1M与RBFA促进的部分未折叠 rRNA h45 结合，而mRNA通道被阻断。这使得METTL15的结合能够促进rRNA的进一步成熟和RBFA的大构象变化。新的构象允许起始因子mtIF3在组装过程中已经占据了亚基界面。

最后，线粒体特异性核糖体蛋白mS37比RBFA更易与SSU-mS37-mtIF3复合物完成组装，该复合物与mtIF2结合并启动翻译。他们的研究结果解释了步骤特异性因子的作用如何调节SSU的动态组装，以及对独特蛋白质mS37的适应，将组装与启动建立催化的线粒体核糖体联系起来。

据介绍，线粒体核糖体是合成和维持生物能量蛋白质所必需的。

附：英文原文

Title: Mechanism of mitoribosomal small subunit biogenesis and preinitiation

Author: Itoh, Yuzuru, Khawaja, Anas, Laptev, Ivan, Cipullo, Miriam, Atanassov, Ilian, Sergiev, Petr, Rorbach, Joanna, Amunts, Alexey

Issue&Volume: 2022-06-08

Abstract: Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.

DOI: 10.1038/s41586-022-04795-x

Source: https://www.nature.com/articles/s41586-022-04795-x

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