Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18413-8. doi: 10.1073/pnas.1216730109. Epub 2012 Oct 22.
Eukaryotic translation termination results from the complex functional interplay between two eukaryotic release factors, eRF1 and eRF3, and the ribosome, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, using cryo-electron microscopy (cryo-EM) and flexible fitting, we determined the structure of eRF1-eRF3-guanosine 5'-[β,γ-imido]triphosphate (GMPPNP)-bound ribosomal pretermination complex (pre-TC), which corresponds to the initial, pre-GTP hydrolysis stage of factor attachment. Our results show that eukaryotic translation termination involves a network of interactions between the two release factors and the ribosome. Our structure provides mechanistic insight into the coordination between GTP hydrolysis by eRF3 and subsequent peptide release by eRF1.
真核翻译终止是由两种真核释放因子,eRF1 和 eRF3,以及核糖体之间复杂的功能相互作用导致的,其中 eRF3 的 GTP 水解将密码子识别与 eRF1 介导的肽酰-tRNA 水解偶联。在这里,我们使用冷冻电镜(cryo-EM)和柔性拟合技术,确定了 eRF1-eRF3-鸟苷 5'-[β,γ-亚氨基]三磷酸(GMPPNP)结合的核糖体预终止复合物(pre-TC)的结构,该结构对应于因子结合的初始、预-GTP 水解阶段。我们的结果表明,真核翻译终止涉及到两种释放因子和核糖体之间的相互作用网络。我们的结构为 eRF3 的 GTP 水解和随后的 eRF1 介导的肽释放之间的协调提供了机制上的见解。