Mechanism of chaperonin-mediated protein folding and assembly (A12)

相当一部分新合成的蛋白质需要分子伴侣的帮助才能有效地在生物相关的时间尺度上达到折叠状态。在第二个资助期，我们使用光谱方法和冷冻电子显微镜相结合的方法分析了真核细胞伴侣蛋白trl/cct促进蛋白质折叠的机制，并将蛋白Hgh1表征为一种与trE合作的新伴侣。我们现在计划研究主要的伴侣Hsp70在蛋白质折叠中的功能。我们将使用生物物理技术，如spFRET和H/DX-MS来研究Hsp70是否和伴侣蛋白一样，可以加速折叠，如果是，通过什么机制。

A substantial fraction of newly-synthesised proteins require assistance from molecular chaperones to reach their folded states efficiently and at a biologically relevant time scale. In the second funding period, we used a combination of spectroscopic methods and cryo-electron microscopy to analyse the mechanism of the eukaryotic chaperonin TRiC/CCT in promoting protein folding and characterised the protein Hgh1 as a new chaperone that cooperates with TRiC. We now plan to investigate the function of the major chaperone Hsp70 in protein folding. We will use biophysical techniques such as spFRET and H/DX-MS to investigate whether Hsp70, like the chaperonins, can accelerate folding and, if so, by which mechanism.