Analyses of physiological functions of super-disordered proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19246
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Nakagawa Shinichi 北海道大学, 薬学研究院, 教授 (50324679)
• Co-Investigator(Kenkyū-buntansha): 泊 幸秀 東京大学, 定量生命科学研究所, 教授 (90447368)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 超天然変性タンパク質 / 変異マウス / 胎生致死

Outline of Final Research Achievements

It has long been thought that the function of a protein is determined by its specific three-dimensional structure. However, it is becoming clear that there are many "intrinsically disordered proteins" within the genome, which have sequences that make it difficult to adopt a specific structure throughout their entire length. These proteins lack any known functional domains, making it impossible to predict what physiological functions they perform. Therefore, in this study, we created mutant mice lacking these functionally uncharacterized intrinsically disordered proteins to investigate their physiological roles. As a result, we found that mutations in at least four types of these proteins cause embryonic lethality, indicating that they perform crucial physiological functions.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

様々な生物のゲノム配列が明らかとなるにつれて、生物を作るためのパーツの記載は終了した、これからはシステムを理解する時代だ、と言われるようになりました。ところが、ゲノムの中には配列からは機能を予測することが出来ないタンパク質がまだまだ残されています。我々はそれらの中でも特に特定の立体構造を取りにくいタンパク質を「超天然変性タンパク質」と呼んでいますが、今回の研究で、それらのタンパク質にも重要な生理機能があることが明らかとなりました。今後はこれら超天然変性タンパク質の機能を理解し、さらに応用へとつなげることで、従来型のタンパク質では不可能であった新たな分子操作技術の開発が期待されます。