Translational control of protein folding by elongation kinetics (B14*)

通过延伸动力学翻译控制蛋白质折叠 (B14*)

• 批准号: 447463583
• 金额: --
• 依托单位: Max-Planck-Institut für Biochemie (MPIB)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/447463583?language=en
• 关键词: Translational; control; protein; folding; elongation

Many proteins begin to fold as they emerge from translating ribosomes. The interplay between synonymous codon choice and matching tRNA supply can promote folding by modulating local translation rates, but the underlying regulatory principles are largely unknown. In this project, we will combine ribosome profiling with limited proteolysis mass spectrometry (LiP MS) to define how changes in tRNA or co translational chaperone availability impact translation and protein conformation landscapes in yeast. This global approach will identify proteins with folding trajectories potentially modulated by elongation kinetics in vivo and help uncover underlying mRNA sequence and protein structure patterns. We will explore the nature and origins of conformational changes stemming from altered translation rates for a subset of proteins with biophysical methods.

许多蛋白质在翻译核糖体后开始折叠。同义密码子选择和匹配tRNA供应之间的相互作用可以通过调节局部翻译速率来促进折叠，但潜在的调节原理在很大程度上是未知的。在这个项目中，我们将结合核糖体分析和有限蛋白水解质谱（LiP MS）来定义tRNA或共翻译伴侣可用性的变化如何影响酵母的翻译和蛋白质构象景观。这种全球性的方法将识别体内可能由伸长动力学调节的折叠轨迹的蛋白质，并有助于揭示潜在的mRNA序列和蛋白质结构模式。我们将探索的性质和起源构象变化源于改变翻译率的蛋白质子集与生物物理方法。