2016 Fiscal Year Final Research Report
Structural analysis of selenoprotein P as a diabetes-associated hepatokine
| Project/Area Number |
26461328
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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 |
Metabolomics
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | セレノプロテインP / ヘパトカイン / 結晶構造解析 / ホモロジーモデリング / LDL受容体ファミリー / タンパク質相互作用解析 |
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| Outline of Final Research Achievements |
Selenoprotein P (SeP) is a diabetes-associated hepatokine. Structure based drug design for SeP should be one of useful techniques for screening new compounds as potential anti-diabetic drugs.
To solve the crystal structure, we have established a purification protocol of SeP from human plasma. In addition, we have established a expression and purification protocol of cysteine-substituted SeP. A homology modeling revealed that the N-terminal domain of SeP has a characteristic tertiary structure termed the thioredoxin fold, except a insertion of long loop. Such insertion may be a receptor-interacting region.
Also, we found that LRP1 is a SeP receptor in the muscle and SeP causes exercise resistance through LRP1. Biacore analysis showed that SeP specifically binds one of ligand binding domains of LRP1. Detailed analysis is now in progress.
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| Free Research Field |
分子糖尿病学、構造生命科学
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