Biochemiezentrum der Universität Heidelberg (BZH), INF 328, D-69120, Heidelberg, Germany.
Zentrum für Molekulare Biologie der Universität Heidelberg, INF282, D-69120, Heidelberg, Germany.
Nat Commun. 2020 Feb 7;11(1):776. doi: 10.1038/s41467-020-14603-7.
Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays an important role in cancer regulation. Ebp1 shares the methionine aminopeptidase (MetAP) fold and binds to mature 80S ribosomes for translational control. Here, we present a cryo-EM single particle analysis reconstruction of Ebp1 bound to non-translating human 80S ribosomes at a resolution range from 3.3 to ~8 Å. Ebp1 blocks the tunnel exit with major interactions to the general uL23/uL29 docking site for nascent chain-associated factors complemented by eukaryote-specific eL19 and rRNA helix H59. H59 is defined as dynamic adaptor undergoing significant remodeling upon Ebp1 binding. Ebp1 recruits rRNA expansion segment ES27L to the tunnel exit via specific interactions with rRNA consensus sequences. The Ebp1-ribosome complex serves as a template for MetAP binding and provides insights into the structural principles for spatial coordination of co-translational events and molecular triage at the ribosomal tunnel exit.
人 Ebp1 是增殖相关 2G4（PA2G4）家族的成员，在癌症调控中发挥重要作用。Ebp1 具有蛋氨酸氨肽酶（MetAP）折叠结构，并与成熟的 80S 核糖体结合以进行翻译控制。在这里，我们呈现了一个 cryo-EM 单颗粒分析重建的 Ebp1 与非翻译的人 80S 核糖体结合的结构，分辨率范围从 3.3 到~8Å。Ebp1 通过与新生链相关因子的通用 uL23/uL29 对接位点的主要相互作用来封锁隧道出口，这些因子由真核生物特异性的 eL19 和 rRNA 螺旋 H59 补充。H59 被定义为动态接头，在与 Ebp1 结合时会发生显著的重塑。Ebp1 通过与 rRNA 保守序列的特异性相互作用将 rRNA 扩展片段 ES27L 招募到隧道出口。Ebp1-核糖体复合物可作为 MetAP 结合的模板，并为核糖体隧道出口处共翻译事件的空间协调和分子分类的结构原理提供了见解。
