Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nucleic Acids Res. 2012 Oct;40(18):9319-28. doi: 10.1093/nar/gks660. Epub 2012 Jul 5.
When a stop codon appears at the ribosomal A site, the class I and II release factors (RFs) terminate translation. In eukaryotes and archaea, the class I and II RFs form a heterodimeric complex, and complete the overall translation termination process in a GTP-dependent manner. However, the structural mechanism of the translation termination by the class I and II RF complex remains unresolved. In archaea, archaeal elongation factor 1 alpha (aEF1α), a carrier GTPase for tRNA, acts as a class II RF by forming a heterodimeric complex with archaeal RF1 (aRF1). We report the crystal structure of the aRF1·aEF1α complex, the first active class I and II RF complex. This structure remarkably resembles the tRNA·EF-Tu complex, suggesting that aRF1 is efficiently delivered to the ribosomal A site, by mimicking tRNA. It provides insights into the mechanism that couples GTP hydrolysis by the class II RF to stop codon recognition and peptidyl-tRNA hydrolysis by the class I RF. We discuss the different mechanisms by which aEF1α recognizes aRF1 and aPelota, another aRF1-related protein and molecular evolution of the three functions of aEF1α.
当核糖体 A 位出现终止密码子时，I 类和 II 类释放因子（RFs）终止翻译。在真核生物和古菌中，I 类和 II 类 RF 形成异二聚体复合物，以 GTP 依赖性方式完成整个翻译终止过程。然而，I 类和 II 类 RF 复合物的翻译终止结构机制仍未解决。在古菌中，延伸因子 1α（aEF1α）是 tRNA 的载体 GTPase，通过与古菌 RF1（aRF1）形成异二聚体复合物，充当 II 类 RF。我们报告了 aRF1·aEF1α 复合物的晶体结构，这是第一个活性的 I 类和 II 类 RF 复合物。该结构与 tRNA·EF-Tu 复合物非常相似，表明 aRF1 通过模拟 tRNA 有效地被递送到核糖体 A 位。它为将 II 类 RF 的 GTP 水解与终止密码子识别和 I 类 RF 的肽酰-tRNA 水解偶联的机制提供了见解。我们讨论了 aEF1α 识别 aRF1 和另一种 aRF1 相关蛋白 aPelota 以及 aEF1α 的三种功能的分子进化的不同机制。
