Generation of atomic model of more intact doublet microtubule structure

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15733
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Ichikawa Muneyoshi 奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (80844662)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ダイニン / 繊毛 / クライオ電子顕微鏡法

Outline of Final Research Achievements

Cilia are tiny hair-like structures that drive cell motility. There are nine doublet microtubules in cilia, and axonemal dynein, a motor protein, is periodically bound to these doublet microtubules. Among axonemal dynein, outer-arm dynein is the main motor that produces ciliary motion. Outer arm dynein is a complex composed of many subunits, but the details of the structure of outer arm dynein bound to doublet microtubules were to be eluciated. In this study, subunit structure of the outer-arm dynein complex bound to the doublet microtubule was obtained by cryo-electron microscopy. Furthermore, by comparing the structure of the outer arm dynein complex with that of the inactive outer arm dynein complex before its incorporation into the cilia, the activation mechanisms of outer arm dynein was revealed.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

繊毛は、ヒトの体内のほぼ全ての細胞に存在しており、繊毛タンパク質の異常は、内蔵逆位や不妊などヒトにおける繊毛病の症状を引き起こすことも知られている。そのため、繊毛の運動機構の理解は重要な課題である。本研究において繊毛内の外腕ダイニンの立体構造及び活性化機構を解明できたことは、これらの繊毛病の病態の理解に重要な基盤となる。また、本研究において明らかになった外腕ダイニンの高分解能の構造は、今後、外腕ダイニンを改変し、新たなナノデバイスを開発することにも応用できるだろう。