| Budget Amount *help |
¥115,700,000 (Direct Cost: ¥89,000,000、Indirect Cost: ¥26,700,000)
Fiscal Year 2018: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2017: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2016: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2015: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2014: ¥34,580,000 (Direct Cost: ¥26,600,000、Indirect Cost: ¥7,980,000)
|
|---|
| Outline of Final Research Achievements |
Disulfide bond formation is a crucial step in the folding of numerous cell-surface proteins. Here, we developed a system to study the cotranslational folding of a cell-surface multidomain protein, LDL receptor. Using the system, we found that isomerization of nonnative disulfides to native ones, a key step in the folding of many cell-surface proteins, takes place at a specific timing during synthesis in a manner dependent of a downstream region of the polypeptide. Thus, folding of multidomain proteins in the ER may be more coordinated and elaborated than thought. We also succeeded in single-molecule observation of PDI engaged in the catalysis of oxidative protein folding using high-speed atomic force microscopy. Consequently, we discovered that PDI dimerizes in a substrate-dependent manner and catalyzes its oxidative folding in the central cavity of the dimer. These findings provide a number of new insights into the disulfide bond formation system of mammalian cells.
|
