2018 Fiscal Year Final Research Report
Chemical approaches towards ER endomannosidase contributing degradation of misfolded glycoprotein
| Project/Area Number |
16K01938
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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 |
Chemical biology
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| Research Institution | Seikei University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 糖鎖 / 酵素 / 合成化学 / タンパク質品質管理 |
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| Outline of Final Research Achievements |
In order to elucidate the function of endomannosidase (ER-EM) activity involved in the degradation mechanism in glycoprotein quality control, we synthesized substrates for the functional analysis of this enzyme using glycans extracted from hen egg yolk. Moreover, we combined blue native PAGE and MS / MS analysis against ER internal proteins and clarified that ER-EM active complex contains Ces1d. Furthermore, development of calreticulin inhibitor, EDEM specificity analysis, and aglycone specificity analysis of ER Glc / Man processing reaction were also performed, that might contributes to ER-EM analysis. In addition, we analyzed the correlation between the operating status of the CNX / CRT cycle, which is the central mechanism of glycoprotein quality control, and the metabolic syndrome.
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| Free Research Field |
糖質化学
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病や糖尿病、骨粗鬆症などのフォールディング病は、細胞内への不良品タンパク質の蓄積が発症の一因となる。したがって小胞体糖タンパク質品質管理において不良糖タンパク質分解を司る仕組みを理解し、制御できれば、これらの疾患の診断や治療に貢献できる。本研究では不良糖タンパク質の分解に寄与するER-EM 活性の活性複合体に含まれる Ces1d を同定し、分解機構の理解に貢献した。また本活性を選択的に計測できる糖鎖基質の開発に成功し、疾患に伴う活性変動分析に寄与する要素技術を確立した。またER-EMと協働する糖タンパク質品質管理関連タンパク質の機能やフォールディング病との相関を明らかにした。
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