Abstract

Class I release factors (RFs) recognize stop codons in the sequences of mRNAs and are required for the hydrolysis of peptidyl-tRNA in the ribosomal P site during the final step of protein synthesis in bacteria, resulting in the release of a complete polypeptide chain from the ribosome. A key role in this process belongs to the highly conserved GGQ motif in RFs. Mutations in this motif can reduce the hydrolysis rate or even completely inhibit the reaction. Previously, it was hypothesized that the amino acid residues of GGQ (especially glutamine) are essential for the proper coordination of the water molecule for subsequent hydrolysis of the ester bond. However, available structures of the 70S ribosome termination complex do not allow unambiguous identification of the exact orientation of the carbonyl group in peptidyl-tRNA relative to the GGQ, as well as of the position of the catalytic water molecule in the peptidyl transferase center (PTC). This mini-review summarizes key facts and hypotheses on the role of GGQ in the catalysis of peptide release, as well as suggests and discusses future experiments aimed to produce high-quality structural data for deciphering the precise mechanism of RF-mediated catalysis.

中文翻译：

---

释放因子在肽基-tRNA 酯键水解中的作用

摘要

I 类释放因子 (RF) 识别 mRNA 序列中的终止密码子，并且是细菌蛋白质合成最后一步中核糖体 P 位点中肽酰-tRNA 水解所必需的，导致从 mRNA 中释放完整的多肽链。核糖体。该过程中的关键作用属于 RF 中高度保守的 GGQ 基序。该基序中的突变可以降低水解速率甚至完全抑制反应。以前，有人假设 GGQ 的氨基酸残基（尤其是谷氨酰胺）对于水分子的适当配位以随后酯键的水解是必不可少的。然而，70S 核糖体终止复合物的可用结构不允许明确鉴定肽基-tRNA 中羰基相对于 GGQ 的确切方向，以及催化水分子在肽基转移酶中心 (PTC) 中的位置。这篇小型综述总结了关于 GGQ 在肽释放催化中作用的关键事实和假设，并建议和讨论了旨在产生高质量结构数据以破译 RF 介导催化的精确机制的未来实验。