Substrate dependent selective recruitment for the co-activators by the use of the structure dynamics of nuclear receptor

2016 Fiscal Year Final Research Report

• Project/Area Number: 26291015
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: Tate Shin-ichi 広島大学, 理学(系)研究科(研究院), 教授 (20216998)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: nuclear receptor / co-activator / transient structure / NMR / structure dynamics / time resolution FRET

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.

Free Research Field

NMR structure biology