Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, USA.
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, USA.
Sci Rep. 2018 Feb 5;8(1):2349. doi: 10.1038/s41598-018-20107-8.
The universally conserved Gly-Gly-Gln (GGQ) tripeptide in release factors or release factor-like surveillance proteins is required to catalyze the release of nascent peptide in the ribosome. The glutamine of the GGQ is methylated post-translationally at the N position in vivo; this covalent modification is essential for optimal cell growth and efficient translation termination. However, the precise conformation of the methylated-GGQ tripeptide in the ribosome remains unknown. Using cryoEM and X-ray crystallography, we report the conformation of methylated-GGQ in the peptidyl transferase center of the ribosome during canonical translational termination and co-translation quality control. It has been suggested that the GGQ motif arose independently through convergent evolution among otherwise unrelated proteins that catalyze peptide release. The requirement for this tripeptide in the highly conserved peptidyl transferase center suggests that the conformation reported here is likely shared during termination of protein synthesis in all domains of life.
普遍保守的释放因子或释放因子样监控蛋白中的 Gly-Gly-Gln (GGQ) 三肽对于催化核糖体中新生肽的释放是必需的。该 GGQ 中的谷氨酰胺在体内的 N 位上发生翻译后甲基化修饰；这种共价修饰对于最佳细胞生长和有效的翻译终止至关重要。然而，核糖体中甲基化-GGQ 三肽的精确构象仍然未知。使用 cryoEM 和 X 射线晶体学，我们报告了在典型翻译终止和共翻译质量控制过程中，甲基化-GGQ 在核糖体肽基转移酶中心的构象。已经有人提出，在催化肽释放的原本不相关的蛋白中，通过趋同进化独立出现了 GGQ 基序。该三肽在高度保守的肽基转移酶中心的需求表明，在所有生命领域的蛋白质合成终止过程中，这里报告的构象可能是共同的。
