Principles of molecular motor proteins

Molecular motor proteins support life, and are far superior to synthetic molecular machines in many aspects [1-3]. In order to clarify their operational and design principles, we investigate the motion and function of individual molecular motor proteins, and engineer molecular motor proteins that do not exist in nature [4].


[1] Iino R et al, Chemical Reviews (2020) "Introduction: Molecular Motors"
[2] The Nobel Prize in Chemistry 2016 "The design and synthesis of molecular machines"
[3] Peplow M, Nature (2015) "The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps"
  日本語訳: 分子マシンの時代がやってきた(Natureダイジェスト 2015年12月号)
[4] An Interview posted on the website of IMS (April 2, 2020) 日本語版
[5] 飯野亮太 現代化学 2021年7月号「生体分子モーターの予想外の動きを観る
[6] 飯野亮太 生物物理 2021年61巻2号「いきものが機械でもいいじゃない

Understand molecular motor proteins

We unveil operational principles of molecular motor proteins. We are studying linear [1-9] and rotary molecular motors [10-12] which generate mechanical forces and torques from chemical energy or electrochemical potential. Especially, we focus on new molecular motors such as chitinasescellulases and V-ATPases. Our study is based on state-of-the-art single-molecule imaging.

We are developing new single-molecule methods such as high-speed/high-precision imaging with plasmonic nanoprobes [3, 8-10, 12-15]. We also collaborate with Prof. Takayuni Uchihashi (Nagoya Univ) for single-molecule imaging with high-speed AFM [16] and development of hybrid instruments [17]. We also determine structures of molecular motor proteins by using X-ray crystallography [3] and cryo-EM single-particle analysis by collaborations with Prof. Akihiko Nakamura (Shizuoka Univ) and Prof. Kazuyoshi Murata (ExCELLS), respectively.


私たちは光学顕微鏡1分子計測を分子モーターの解析に駆使します。プラズモニックナノプローブ高速・高精度1分子計測の開発を行っています[3, 8-10, 12-15]。また、内橋貴之さん(名大)との共同研究で高速AFM1分子計測[16]や光学顕微鏡・高速AFM複合機[17]の開発も行っています。さらに、中村彰彦さん(静岡大)とX線結晶構造解析[3]、村田和義さん(ExCELLS)とクライオ電顕単粒子解析[11]、岡崎圭一さん(分子研)とMDや数理シミュレーション[2]の共同研究を行っています。

[1] J Biol Chem 2020, [2] J Phys Chem 2020 (Press release), [3] Nat Commun. 2018, [4] PCCP 2018 (Backcover), [5] J Biol Chem 2020 (Press release), [6] J Biol Chem 2016 (Cover), [7] J Biol Chem 2014, [8] Sci Rep 2020 (Press release), [9] Nat Chem Biol 2016, [10] J Biol Chem 2019 (Press release), [11] Sci Rep 2018, [12] J Biol Chem 2014, [13] Biophys J 2018 (Press release), [14] ACS Photonics2019 (Press release), [15] Anal Chem 2015, [16] Nat Commun. 2018, [17] BBA Gen Sub 2020

Engineer molecular motor proteins and enzymes

To understand their design principles, we engineer molecular motor proteins by using saturation mutagenesis and robot-based automation [18, 19], hybridization [20], and computational design [21, 22]. Computational design is conducted by collaboration with Prof. Nobuyasu Koga and Prof. Takahiro Kosugi (IMS). Recently, we have also been engineering industrially important enzymes, and have succeeded in improvement of thermostability and catalytic activity of a PET hydrolase [23].

私たちは天然に存在しないタンパク質分子モーターをつくることにチャレンジしています。網羅的変異体作製ロボットによる自動化[18, 19]、異種分子間のハイブリッド化[20]、計算科学による合理設計[21, 22]を駆使し、タンパク質分子モーターを改造してその設計原理を理解します。合理設計は古賀信康さん、小杉貴洋さん(分子研)との共同研究で進めています。最近は産業において重要な酵素の改変にも取り組んでおり、PET分解酵素の熱安定性と活性の向上に成功しています[23]。

[18] ACS Omega 2020, [19] ACS Omega 2018, [20] PNAS 2016, [21] Biochemistry 2015, [22] bioRxiv 2020, [23] ACS Catalysis 2021