| Budget Amount *help |
¥43,810,000 (Direct Cost: ¥33,700,000、Indirect Cost: ¥10,110,000)
Fiscal Year 2021: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2020: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2019: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2018: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
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| Outline of Final Research Achievements |
In this study, we analyzed the three-dimensional structure of the epilepsy-associated protein complex LGI1-ADAM22-PSD-95 to understand the mechanism of signal transduction through the membrane and pathogenesis. We revealed the details of the interaction mode between LGI1 and ADAM22 by the integrated structure analysis combining X-ray crystallography, X-ray small-angle scattering analysis, and cryo-electron microscopy. Furthermore, we showed that a mutation in LGI1 whose pathogenic mechanism was unknown causes abnormalities in the formation of higher-order assembly of LGI1-ADAM22, using a mouse model. In addition, we contributed to the elucidation of the molecular mechanism underlying the molecular condensation of PSD-95 induced by LGI1-ADAM22 and the regulation of the amount of ADAM22 by 14-3-3 protein.
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