2025/10/15
生化所徐尚德老師實驗室最新發表刊登於 Nucleic Acids Research
徐尚德老師實驗室揭示一種人工設計的核醣體停滯肽段（eRAP）如何精準控制蛋白質合成的節奏，說明細胞內「暫停鍵」的分子機制。
研究成果刊登於 Nucleic Acids Research
研究團隊運用高解析度冷凍電子顯微鏡（cryo-EM）觀察到，eRAP 同時結合了兩種天然停滯系統的特性——對色胺酸敏感的 TnaC 與對紅黴素反應的 ErmCL——形成一種能更有效暫停核醣體的混合型肽段。
結構分析顯示，eRAP 與核醣體 RNA 與蛋白質在出口通道內形成特定接觸，引發細微構形變化以暫停翻譯。研究亦發現，新生蛋白會與伴護蛋白 Trigger Factor 互動，促進其在離開核醣體時即形成較長的螺旋結構。
此成果不僅揭示核醣體自我調控的分子基礎，亦為精準調控蛋白質合成與新型抗生素設計提供新的研究方向。
New publication from Academia Sinica!
Danny Hsu’s team at Academia Sinica has uncovered how an engineered ribosome arrest peptide (eRAP) can precisely control the rhythm of protein synthesis — shedding light on the cell’s own “pause button” during translation.
Read the paper in Nucleic Acids Research
Using high-resolution cryo-electron microscopy (cryo-EM), the researchers visualized how eRAP interacts with the ribosome to temporarily halt protein production. Remarkably, eRAP combines the functional features of two natural stalling systems — TnaC, which responds to tryptophan, and ErmCL, which reacts to the antibiotic erythromycin — creating a hybrid peptide capable of pausing the ribosome with exceptional precision.
Their structural analyses revealed that eRAP forms specific contacts with ribosomal RNA and proteins in the exit tunnel, triggering subtle conformational changes that stop translation. The team also discovered that the newly synthesized protein interacts with the chaperone Trigger Factor, promoting early folding into an extended helical structure as it emerges from the ribosome.
This study not only reveals the molecular basis of ribosome pausing but also opens new directions for precise control of protein synthesis and next-generation antibiotic design.
