Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
Department of Cell Biology, Harvard Medical School, Boston, United States.
Elife. 2018 Oct 24;7:e40486. doi: 10.7554/eLife.40486.
The cellular levels and activities of ribosomes directly regulate gene expression during numerous physiological processes. The mechanisms that globally repress translation are incompletely understood. Here, we use electron cryomicroscopy to analyze inactive ribosomes isolated from mammalian reticulocytes, the penultimate stage of red blood cell differentiation. We identify two types of ribosomes that are translationally repressed by protein interactions. The first comprises ribosomes sequestered with elongation factor 2 (eEF2) by SERPINE mRNA binding protein 1 (SERBP1) occupying the ribosomal mRNA entrance channel. The second type are translationally repressed by a novel ribosome-binding protein, interferon-related developmental regulator 2 (IFRD2), which spans the P and E sites and inserts a C-terminal helix into the mRNA exit channel to preclude translation. IFRD2 binds ribosomes with a tRNA occupying a noncanonical binding site, the 'Z site', on the ribosome. These structures provide functional insights into how ribosomal interactions may suppress translation to regulate gene expression.
核糖体的细胞水平和活性在众多生理过程中直接调节基因表达。全面抑制翻译的机制尚未完全了解。在这里，我们使用电子冷冻显微镜分析从哺乳动物网织红细胞（红细胞分化的倒数第二阶段）中分离出的无活性核糖体。我们鉴定出两种因蛋白质相互作用而翻译受抑制的核糖体。第一种包括被丝氨酸蛋白酶抑制剂mRNA结合蛋白1（SERBP1）隔离的核糖体，SERBP1占据核糖体mRNA进入通道，与延伸因子2（eEF2）结合。第二种类型的核糖体被一种新型核糖体结合蛋白——干扰素相关发育调节因子2（IFRD2）翻译抑制，IFRD2跨越P位和E位，并将一个C末端螺旋插入mRNA出口通道以阻止翻译。IFRD2与一个占据核糖体上非经典结合位点“Z位”的tRNA结合核糖体。这些结构为核糖体相互作用如何抑制翻译以调节基因表达提供了功能见解。
