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

许多蛋白质在翻译核糖体时开始折叠。同义密码子选择和匹配的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，但潜在的调控原理在很大程度上尚不清楚。在这个项目中，我们将结合核糖体图谱和有限蛋白分解质谱仪(LIP MS)来定义tRNA或共翻译伴侣蛋白可用性的变化如何影响酵母中的翻译和蛋白质构象。这一全球方法将识别具有可能受体内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。我们将用生物物理的方法探索由于蛋白质子集的翻译速率改变而引起的构象变化的性质和起源。

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.