Quality control mechanism of misfolded proteins

我们的研究是通过关注内质网（ER）中蛋白质质量控制的两个问题来进行的。第一个是关于ER中分子伴侣和氧化还原酶对新生多肽的生产性折叠。二是揭示ER相关降解（ERAD）系统消除ER中错误折叠蛋白质的质量控制机制。我们发现了两个新的ERAD因子，EDEM 1和ERdj 5。在这方面，主要讨论了关于这一建议的三个问题：1）我们成功地解决了ERdj 5的晶体结构，该ERdj 5还原了待降解的错误折叠蛋白质中的二硫键，并提出了糖蛋白ERAD系统中的底物转移途径，2）我们揭示了错误折叠非糖基化蛋白质的新ERAD途径，（3）揭示了Ero 1a、PDI和ERp46在氧化过程中的电子传递途径。

Our study was performed by focusing two issues in protein quality control in the endoplasmic reticulum (ER). The first one was on the productive folding of nascent polypeptides by molecular chaperones and oxidoredcutases in the ER. The second one was to reveal the quality control mechanism of ER-associated degradation (ERAD) system that eliminates the misfolded proteins from the ER. We found two novel factors involved in the ERAD, EDEM1 and ERdj5. In this term, mainly three issues on this proposal was addressed: 1) we succeeded to solve the crystal structure of ERdj5 that reduces the disulfide bonds in the misfolded proteins to be degraded and proposed the substrate transfer pathway in the ERAD system for glycoproteins, 2) we revealed the novel ERAD pathway for misfolded non-glycosylated proteins, and 3) we showed the electron transfer pathway in the process of oxidation including Ero1a, PDI and ERp46.