Structure and function relationship of retrovirus envelope protein that induces epithelial cell transformation
| Project/Area Number |
17K08848
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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 |
Virology
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| Research Institution | Hokkaido University |
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Principal Investigator |
MAEDA Naoyoshi 北海道大学, 薬学研究院, 特任准教授 (80444800)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | レトロウイルス / JSRV / ENTV / トランスフォーメーション / 腫瘍 / タンパク質 / 構造解析 / 宿主因子 / ウィルス / 癌 / 細胞・組織 / シグナル伝達 / 蛋白質 |
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| Outline of Final Research Achievements |
JSRV Envelope (Env) functions as a dominant oncoprotein in transforming fibroblast and epithelial cells. Several candidates for interacting partners of the Env CT region have been found in MALDI-TOF MS analysis. One candidate is vimentin, a major intermediate filament protein. Their interaction was confirmed by multiple assays. Vimentin on the cell surface co-localized with Env in transformed cells. In addition, a vimentin inhibitor inhibited transformation by the JSRV Env in a dose-dependent manner.
The Env SU domain has been shown to form a complex consisting of several dimers or trimers. CD spectroscopic analysis revealed that the SU domain has about 34% beta-sheet, 3.8% alpha-helix, and 15% turn. Further, the structure of the SU domain has been observed by transmission electron microscopy and cryo-electron microscopy, which showed that the SU protein complex looks like a
bunch of mushrooms, consisting of a head domain and a string domain.
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| Academic Significance and Societal Importance of the Research Achievements |
エンベロープは本来、標的細胞への侵入の際に機能するウイルス膜タンパク質であるが、JSRV/ENTVエンベロープはがん遺伝子としても機能することで呼吸器系の上皮細胞を腫瘍化し、腺がんを発症させる極めてまれな題材であり、腫瘍ウイルス学の発展に寄与することができる学術的価値を有している。またJSRVとENTVのエンベロープは、GPIアンカー型分子Hyal-2 を受容体として細胞侵入時に使用するにもかかわらず、ヒツジ個体で腫瘍発生器官を異にすることから、「ウイルス感染→細胞指向性→発がん」を研究する上で理想的なモデルになる。また、エンベロープの構造機能相関の解明は、有効な治療法やワクチン開発に繋がる。
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Report
(4 results)
Research Products
(11 results)
