Elucidating the effects of microtubule inner proteins on the architecture of the tubulin lattice.

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23726
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• 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): 2019-08-30 – 2021-03-31
• Keywords: 繊毛 / ダブレット微小管 / 微小管内タンパク質 / クライオ電子顕微鏡 / X線結晶構造解析

Outline of Final Research Achievements

By obtaining high resolution structures of the doublet microtubule from cilia, detailed binding schemes of the microtubule inner proteins (MIPs) to the tubulin lattice have been revealed. By comparing the tubulin lattice with intact MIPs with the one with some MIPs missing, it was shown that the MIPs fix the tubulin lattice length into the stable elongated conformation. MIPs were also shown to change the angles between the protofilaments. Some of the protein identities of these MIPs were identified by mass spectrometry and X-ray crystal structures were obtained. Co-polymerization experiments of the MIP proteins and tubulins were also performed and the effects of the MIPs on the tubulin lattice formation from the inside have also been revealed.

Free Research Field

構造生命科学・生物物理学

Academic Significance and Societal Importance of the Research Achievements

繊毛はヒトの体内においても多彩な機能を担う重要な構造体である。気管の上皮でウイルスなどの異物を除去するなど重要な機能を担っている。繊毛は１秒間に数十回波打つために安定かつしなやかな性質をもつが、繊毛がどのようにしてこのような特性を得ているかはわかっていなかった。本研究では、繊毛内のダブレット微小管がどのようにして安定化されるかを初めて示すことができた。これは、ヒトの繊毛病の病態が引き起こされる機構の理解や、将来的にはその治療にも応用できる可能性のある重要な知見である。