Chaperone-assisted protein folding in the bacterial periplasm

分子伴侣帮助几乎所有细胞蛋白质的折叠。尽管进行了多年的密集研究，但伴侣如何促进蛋白质折叠的根本问题仍然不清楚。虽然细胞质中的分子伴侣利用ATP水解的能量来控制底物的结合、折叠和释放，但在缺乏ATP的情况下，细菌周质中的分子伴侣如何帮助折叠尚不清楚。最近的实验已经确定了周质伴侣Spy、Skp和Sura的底物。其中一些伴侣帮助水溶性和膜蛋白的折叠，提出了一些有趣的问题，即伴侣如何能够识别其底物，以受控的方式释放它们，并帮助折叠。在这个项目中，学生将使用生化和生物物理方法来确定周质分子伴侣如何识别它们的底物，帮助折叠，并与彼此和Bam复合体一起，创建细菌生长和生存所需的折叠管道。

Molecular chaperones assist the folding of virtually all cellular proteins. Despite years of intensive study, the fundamental question of how chaperones facilitate protein folding remains unclear. Whilst molecular chaperones in the cytosol use the energy of ATP hydrolysis to control substrate binding, folding and release, how chaperones in the bacterial periplasm assist folding in the absence of ATP is unknown. Recent experiments have identified the substrates of the periplasmic chaperones Spy, Skp and SurA. Some of these chaperones assist folding of both water-soluble and membrane proteins, raising fascinating questions about how a chaperone is able to recognize its substrates, to release them in a controlled fashion and to assist folding. In this project the student will use biochemical and biophysical methods to determine how periplasmic molecular chaperones recognize their substrates, assist folding and, in tandem with each other and the Bam complex, create the folding pipeline required for bacterial growth and survival.