Updated on 2023/09/29

写真a

 
TANAKA Kotaro
 
Organization
Cellular and Structural Physiology Institute Division Assistant Professor
Graduate School
Graduate School of Pharmaceutical Sciences
Title
Assistant Professor
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Degree 1

  1. 博士(理学) ( 2019.2   名古屋大学 ) 

Research Areas 1

  1. Life Science / Structural biochemistry

Research History 1

  1. Kyushu Institute of Technology   Faculty of Computer Science and Systems Engineering

    2019.4 - 2021.5

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    Country:Japan

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Papers 5

  1. Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding Reviewed

    Shota Suzuki, Kotaro Tanaka, Kouki Nishikawa, Hiroshi Suzuki, Atsunori Oshima, Yoshinori Fujiyoshi

    Nature Communications   Vol. 14 ( 1 )   2023.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.

    DOI: 10.1038/s41467-023-41650-7

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    Other Link: https://www.nature.com/articles/s41467-023-41650-7

  2. Structures and mechanisms of actin ATP hydrolysis. Reviewed International journal

    Yusuke Kanematsu, Akihiro Narita, Toshiro Oda, Ryotaro Koike, Motonori Ota, Yu Takano, Kei Moritsugu, Ikuko Fujiwara, Kotaro Tanaka, Hideyuki Komatsu, Takayuki Nagae, Nobuhisa Watanabe, Mitsusada Iwasa, Yuichiro Maéda, Shuichi Takeda

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 119 ( 43 ) page: e2122641119   2022.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG-O3B bond cleavage; 3) four concomitant events: W1-PO3- formation, OH- and proton cleavage, nucleophilic attack by the OH- against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi-bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes.

    DOI: 10.1073/pnas.2122641119

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  3. Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM Reviewed International journal

    Shota Suzuki, Momoko Iida, Yoko Hiroaki, Kotaro Tanaka, Akihiro Kawamoto, Takayuki Kato, Atsunori Oshima

    Communications Biology   Vol. 5 ( 707 ) page: 707 - 707   2022.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    MrgD, a member of the Mas-related G protein-coupled receptor (MRGPR) family, has high basal activity for Gi activation. It recognizes endogenous ligands, such as β-alanine, and is involved in pain and itch signaling. The lack of a high-resolution structure for MrgD hinders our understanding of whether its activation is ligand-dependent or constitutive. Here, we report two cryo-EM structures of the MrgD-Gi complex in the β-alanine-bound and apo states at 3.1 Å and 2.8 Å resolution, respectively. These structures show that β-alanine is bound to a shallow pocket at the extracellular domains. The extracellular half of the sixth transmembrane helix undergoes a significant movement and is tightly packed into the third transmembrane helix through hydrophobic residues, creating the active form. Our structures demonstrate a structural basis for the characteristic ligand recognition of MrgD. These findings provide a framework to guide drug designs targeting the MrgD receptor.

    DOI: 10.1038/s42003-022-03668-3

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    Other Link: https://www.nature.com/articles/s42003-022-03668-3

  4. 巨大システムとしてのクライオ電子顕微鏡法の自動化から自働化への展開

    安永 卓生, 田中 康太郎, 岩嵜 彩夏, 塚本 崇文, 本多 康久

    顕微鏡   Vol. 56 ( 1 ) page: 43 - 47   2021.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

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  5. Trends in Deep Learning Approaches for Protein Structure Classification in Single Particle Analysis

    Nobuya Mamizu, Kotaro Tanaka, Takuo Yasunaga

    KENBIKYO     2020.12

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    Language:Japanese  

Books 1

  1. クライオ電子顕微鏡ハンドブック

    成田哲博, 田中康太郎( Role: Contributor ,  第4章第2節 クライオ電子顕微鏡と単粒子解析による線維構造解析)

    (株)エヌ・ティー・エス  2023.1  ( ISBN:978-4-86043-804-3

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    Total pages:460   Responsible for pages:127-135   Language:Japanese Book type:Scholarly book

Presentations 1

  1. クライオ電子顕微鏡法によるタンパク質構造決定におけるスーパーコンピュータ「不老」の活用検討 Invited

    田中康太郎

    第4回スーパーコンピュータ「不老」ユーザ会  2023.9.6 

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    Event date: 2023.9

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. Membrane permeation mechanism mediated by large pore channels contributed by phospholipids

    Grant number:23H02418  2023.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

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  2. クライオ電子顕微鏡像の構造多型・揺らぎ解析によるギャップ結合チャネル開閉機構解明

    Grant number:23K14135  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  若手研究

    田中 康太郎

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    コネキシンは脊索動物が持つギャップ結合チャネルで、隣接する2つの細胞の細胞質間をトンネルのように直接接続する膜タンパク質複合体である。本研究はヒト由来コネキシンの脂質二重膜中における立体構造をクライオ電子顕微鏡法により解析し、チャネル開閉の構造基盤を解明することを目指す。チャネル開閉に重要な細胞質側領域はフレキシブルなため、開閉機構を理解するにはその構造多形・揺らぎの可視化が重要である。近年は機械学習・統計的データ分析により電顕画像からタンパク質の構造多型・揺らぎを抽出・可視化する構造解析手法群が発展しつつあり、本研究ではそれらを駆使したコネキシンの構造多形・揺らぎの高分解能可視化に挑戦する。

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  3. Protein Structure Determination by Cryo-EM with Supercomputer Flow

    2022.4 - 2023.3

    Nagoya University, JHPCN  "Collaborative Research Project on Computer Science with High-Performance Computing in Nagoya University 

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    Authorship:Principal investigator 

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