| Project/Area Number |
15K06968
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
IWATA So 京都大学, 大学院医学研究科, 教授 (60452330)
SHIMAMURA Tatsuro 京都大学, 大学院医学研究科, 特定講師 (90391979)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膜タンパク質 / 抗体 / X線結晶構造解析 / 創薬ターゲット / 高脂血症 / 胆汁酸 / トランスポーター / コレステロール / 膜蛋白質 |
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| Outline of Final Research Achievements |
High cholesterol levels greatly increase the risk of cardiovascular disease. By its conversion into bile acids, about 50% of cholesterol is eliminated from the body. However bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine via sodium dependent bile acid transporters. ASBT and NTCP, both of which are SLC10 (Sodium bile acid co-transporter family) members, have received attention as a new target of therapeutic drugs. In this study, our efforts have been devoted to crystallization of the mammalian NTCP in complex with its conformation-specific antibody fragments.
A number of NTCP mutants that show high thermostability and monodispersity on size-exclusion chromatography (SEC) have been isolated. In addition, a total of six clones of antibodies that specifically recognize confomational epitope on the NTCP have been developed. Crystallization screening of the NTCP mutant-Fab complex is currently underway.
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