| Budget Amount *help |
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Outline of Final Research Achievements |
We explored the mechanism of the substrate-dependent selective recruitment of the co-activator to PPARg, a type of nuclear receptor. We determined the solution structure of PPARg in the complex with agonist to demonstrate the relative orientation between H3 and H4 surrounding to the co-activator biding pocket was changed, which have been never found in the X-ray structures.
We analyzed the low-population structure of the fragments having the PPARg binding motifs, LxxLL, in SRC1, a co-activator. We revealed that two fragments had different low population structures at the site of LxxLL motif and the C-terminal parts following the binding motif. We also found the C-terminal low population structures are responsible for the co-activator binding to the PPARg. The dynamic structural properties of SRC1 should determine the substrate-dependent co-activator recruitment to the PPARg.
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