| Project/Area Number |
18K14633
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 43020:Structural biochemistry-related
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 自然免疫受容体 / 免疫活性化 / 糖脂質 / コレステロール / ナノディスク / NMR / 免疫受容体 / 糖脂質認識 / Mincle / リポソーム / 脂質 / 自然免疫 / 相互作用解析 / 相互作用 |
|---|
| Outline of Final Research Achievements |
Mincle is an immune receptor that is expressed in antigen presenting cells, such as dendritic cells, arecognizes trehalose dimycolate (TDM), which is specifically present on the surface of Mycobacterium tuberculosis and cholesterol crystals, and activates immune cells. We previously perofrmed X-ray structural analysis of Mincle to elucidate the recognition mechanism of TDM. However, analysis of glycolipids and cholesterol has not progressed due to their low solubility in water. Therefore, we prepared "nanodiscs" that imitated lipid bilayer membranes containing glycolipids and cholesterol, and conducted binding experiments. As a result, no binding was found in glycolipids containing cholesterol, whereas binding to Mincle was found in those containing glycolipids.
|
| Academic Significance and Societal Importance of the Research Achievements |
免疫受容体のMincleは強力な免疫活性化物質である結核菌表面に存在するTDMと呼ばれる分子と結合する。我々はX線構造解析によりMincleの立体構造を明らかにしたが、TDMの難水溶性のためにどのようにMincleがTDMを認識しているのか不明な点が多かった。今回、我々は実際のTDMが結核菌の表面にある状態を模した脂質二重膜にTDM類似体を埋め込んで、認識機構の解明を進めた。その結果、TDM類似体を含まない脂質二重膜はMincleに結合しなかった一方で、TDM類似体を含むものは結合することがわかった。今後、Mincleの認識機構を詳細に明らかにすることで、効果的な免疫活性化物質の探索を目指す。
|
