| Project/Area Number |
18H02390
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 43020:Structural biochemistry-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Kurisu Genji 大阪大学, 蛋白質研究所, 教授 (90294131)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
|---|
| Keywords | 構造生物学 / 分子モーター / ダイニン / 微小管 / 構造生物化学 / ダイナクチン |
|---|
| Outline of Final Research Achievements |
We attempted to crystallize a complex of dynein stalk-MTBD region with LC1 and the αβ-tubulin dimer, but were unable to determine the structure of the complex, although microcrystals were obtained. Furthermore, the CAP-Gly region of dynactin p150 was also analyzed, after evaluating its interaction with αβ-tubulin dimer, and then the structure of the complex was analyzed by cryo-EM. However again, the structure could not be determined at a high resolution. In the course of these structural analyses, we obtained the crystals of the much better MTBD fusion protein alone, which has high microtubule-binding capacity. In addition, from the structural analysis of the complex of the MTBD region of the outer-arm dynein γ-chain and the light chain LC1, we were able to propose a novel binding mode of MTBD to the microtubule utilizing the flap region.
|
| Academic Significance and Societal Importance of the Research Achievements |
微小管を移動する分子モーターは，プラス端方向に移動するキネシンとマイナス端方向に移動するダイニンの2種類がしられている。キネシンの運動メカニズムについては，複数の視点で非常に詳細な情報が蓄積している。これに対しダイニンは，鞭毛・繊毛運動を駆動し，染色体分離や細胞内輸送を担う非常に重要な生体分子であるにも関わらず，モータードメインの分子サイズが380 kDaと巨大であるため，最近まで原子レベルの構造解明が遅れていた。本研究は理解が遅れていたダイニンの運動機構解明に貢献するものであり，今後の展開も期待できる。
|
