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

新合成的蛋白质的相当大一部分需要分子伴侣的帮助，以有效地达到其折叠状态，并在生物学相关的时间尺度。在第二个资助期，我们使用光谱方法和冷冻电子显微镜的组合来分析真核生物伴侣蛋白TRiC/CCT促进蛋白质折叠的机制，并将蛋白质Hgh 1表征为与TRiC合作的新伴侣蛋白。我们现在计划调查的主要伴侣Hsp 70在蛋白质折叠的功能。我们将使用生物物理技术，如spFRET和H/DX-MS来研究是否Hsp 70，像伴侣蛋白，可以加速折叠，如果是这样，通过何种机制。

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.