Updated on 2025/05/17

写真a

 
Naito Ishimoto
 
Organization
School of Science Department of Science Assistant Professor
Title
Assistant Professor
External link

Degree

  • Doctor of Philosophy (Science) ( 2024.3   Yokohama City University )

Research Interests

  • Membran protein

  • ウイルスタンパク質

  • クライオ電子顕微鏡

  • X線結晶構造解析

  • 構造生物学

Research Areas

  • Life Science / Structural biochemistry

Education

  • Yokohama City University   Graduate School of Medical Life Science

    2021.4 - 2024.3

    　 More details

    Country： Japan

    researchmap

  • Yokohama City University   Graduate School of Medical Life Science

    2019.4 - 2021.3

    　 More details

    Country： Japan

    researchmap

  • Yokohama City University   International College of Arts and Sciences   Department of Medical Life Science

    2015.4 - 2019.3

    　 More details

    Country： Japan

    researchmap

Research History

  • Yokohama City University   School of Science Graduate School of Medical Life Science Department of Medical Life Science   Assistant Professor

    2025.4

    　 More details

  • Imperial College London   Life Sciences   Visiting Researcher

    2024.4 - 2025.3

    　 More details

    Country：United Kingdom

    researchmap

  • Yokohama City University   Graduate School of Medical Life Science

    2024.4 - 2025.3

    　 More details

    Country：Japan

    researchmap

Professional Memberships

Papers

  • Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin. Reviewed International journal

    Naito Ishimoto, Joshua L C Wong, Shan He, Sally Shirran, Olivia Wright-Paramio, Chloe Seddon, Nanki Singh, Carlos Balsalobre, Ravi R Sonani, Abigail Clements, Edward H Egelmane, Gad Frankel, Konstantinos Beis

    Proceedings of the National Academy of Sciences of the United States of America   122 ( 16 )   e2427228122   2025.4

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor-recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals. The reference IncHI1 plasmid R27, isolated from Salmonella enterica serovar Typhi, encodes the conjugative H-pilus subunit TrhA containing 74 residues after cleavage of the signal sequence. Here, we show that the H-pilus forms long filamentous structures that mediate MPF and describe its cryoelectron-microscopic (cryo-EM) structure at 2.2 Å resolution. Like the F pilus, the H-pilin subunits form helical assemblies with phospholipid molecules at a stoichiometric ratio of 1:1. While there were previous reports that the T-pilus from Agrobacterium tumefaciens was composed of cyclic subunits, three recent cryo-EM structures of the T-pilus found no such cyclization. Here, we report that the H-pilin is cyclic, with a covalent bond connecting the peptide backbone between the N and C termini. Both the cryo-EM map and mass spectrometry revealed cleavage of the last five residues of the pilin, followed by cyclization via condensation of the amine and carboxyl residues. Mutagenesis experiments revealed that loss of cyclization abolished pilus biogenesis and efficient plasmid transfer. The cyclic nature of the pilin could stabilize the pilus and may explain the high incidence of IncH plasmid dissemination.

    DOI： 10.1073/pnas.2427228122

    PubMed

    researchmap

  • Cryo-EM structure and evolutionary history of the conjugation surface exclusion protein TraT Reviewed

    Chloe Seddon, Sophia David, Joshua L. C. Wong, Naito Ishimoto, Shan He, Jonathan Bradshaw, Wen Wen Low, Gad Frankel, Konstantinos Beis

    Nature Communications   2025.1

    　More details

    Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-025-55834-w

    researchmap

  • Structural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5 Reviewed

    Tomomi Uchikubo-Kamo, Naito Ishimoto, Haruka Umezawa, Mikako Hirohama, Maasa Ono, Haruka Kawabata, Kenichi Kamata, Mio Ohki, Hisashi Yoshida, Jae-Hyun Park, Jeremy R.H. Tame, Atsushi Kawaguchi, Sam-Yong Park

    Biochemical and Biophysical Research Communications   2024.11

    　More details

    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2024.150952

    researchmap

  • Structural basis for hepatitis B virus restriction by a viral receptor homologue Reviewed

    Kaho Shionoya, Jae-Hyun Park, Toru Ekimoto, Junko S. Takeuchi, Junki Mifune, Takeshi Morita, Naito Ishimoto, Haruka Umezawa, Kenichiro Yamamoto, Chisa Kobayashi, Atsuto Kusunoki, Norimichi Nomura, So Iwata, Masamichi Muramatsu, Jeremy R. H. Tame, Mitsunori Ikeguchi, Sam-Yong Park, Koichi Watashi

    Nature Communications   2024.10

    　More details

    Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-024-53533-6

    researchmap

  • Structural basis of hepatitis B virus receptor binding Reviewed

    Jinta Asami, Jae-Hyun Park, Yayoi Nomura, Chisa Kobayashi, Junki Mifune, Naito Ishimoto, Tomoko Uemura, Kehong Liu, Yumi Sato, Zhikuan Zhang, Masamichi Muramatsu, Takaji Wakita, David Drew, So Iwata, Toshiyuki Shimizu, Koichi Watashi, Sam-Yong Park, Norimichi Nomura, Umeharu Ohto

    Nature Structural & Molecular Biology   2024.3

    　More details

    Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41594-023-01191-5

    researchmap

  • Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2 Reviewed

    Jae-Hyun Park, Kouki Kawakami, Naito Ishimoto, Tatsuya Ikuta, Mio Ohki, Toru Ekimoto, Mitsunori Ikeguchi, Dong-Sun Lee, Young-Ho Lee, Jeremy R. H. Tame, Asuka Inoue, Sam-Yong Park

    Nature Communications   2023.11

    　More details

    Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-023-42764-8

    researchmap

  • Structural basis of CXC chemokine receptor 1 ligand binding and activation Reviewed

    Naito Ishimoto, Jae-Hyun Park, Kouki Kawakami, Michiko Tajiri, Kenji Mizutani, Satoko Akashi, Jeremy R. H. Tame, Asuka Inoue, Sam-Yong Park

    Nature Communications   2023.7

    　More details

    Authorship：Lead author   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-023-39799-2

    researchmap

  • Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface Reviewed

    Yunseok Heo, Naito Ishimoto, Ye-Eun Jeon, Ji-Hye Yun, Mio Ohki, Yuki Anraku, Mina Sasaki, Shunsuke Kita, Hideo Fukuhara, Tatsuya Ikuta, Kouki Kawakami, Asuka Inoue, Katsumi Maenaka, Jeremy R. H. Tame, Weontae Lee, Sam-Yong Park

    PLOS Biology   20 ( 8 )   2022.8

    　More details

    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science ({PLoS})  

    <jats:p>Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer’s disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site. Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison between the activated GALR2 and inactive hβ<jats:sub>2</jats:sub>AR was used to relate galanin binding to the movements of transmembrane (TM) helices and the G-protein interface.</jats:p>

    DOI： 10.1371/journal.pbio.3001714

    researchmap

  • Structural insights into the HBV receptor and bile acid transporter NTCP Reviewed

    Jae-Hyun Park, Masashi Iwamoto, Ji-Hye Yun, Tomomi Uchikubo-Kamo, Donghwan Son, Zeyu Jin, Hisashi Yoshida, Mio Ohki, Naito Ishimoto, Kenji Mizutani, Mizuki Oshima, Masamichi Muramatsu, Takaji Wakita, Mikako Shirouzu, Kehong Liu, Tomoko Uemura, Norimichi Nomura, So Iwata, Koichi Watashi, Jeremy R. H. Tame, Tomohiro Nishizawa, Weontae Lee, Sam-Yong Park

    Nature   2022.5

    　More details

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

    DOI： 10.1038/s41586-022-04857-0

    researchmap

  • Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity. Reviewed International journal

    Yunseok Heo, Eojin Yoon, Ye-Eun Jeon, Ji-Hye Yun, Naito Ishimoto, Hyeonuk Woo, Sam-Yong Park, Ji-Joon Song, Weontae Lee

    eLife   11   2022.4

    　More details

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

    Somatostatin is a peptide hormone that regulates endocrine systems by binding to G-protein-coupled somatostatin receptors. Somatostatin receptor 2 (SSTR2) is a human somatostatin receptor and is highly implicated in hormone disorders, cancers, and neurological diseases. Here, we report the high-resolution cryo-EM structure of full-length human SSTR2 bound to the agonist somatostatin (SST-14) in complex with inhibitory G (Gi) proteins. Our structural and mutagenesis analyses show that seven transmembrane helices form a deep pocket for ligand binding and that SSTR2 recognizes the highly conserved Trp-Lys motif of SST-14 at the bottom of the pocket. Furthermore, our sequence analysis combined with AlphaFold modeled structures of other SSTR isoforms provide a structural basis for the mechanism by which SSTR family proteins specifically interact with their cognate ligands. This work provides the first glimpse into the molecular recognition mechanism of somatostatin receptors and a crucial resource to develop therapeutics targeting somatostatin receptors.

    DOI： 10.7554/eLife.76823

    PubMed

    researchmap

  • Pumping mechanism of NM-R3, a light-driven bacterial chloride importer in the rhodopsin family Reviewed

    Ji-Hye Yun, Mio Ohki, Jae-Hyun Park, Naito Ishimoto, Ayana Sato-Tomita, Wonbin Lee, Zeyu Jin, Jeremy R. H. Tame, Naoya Shibayama, Sam-Yong Park, Weontae Lee

    Science Advances   6 ( 6 )   2020.2

    　More details

    Publishing type：Research paper (scientific journal)   Publisher：American Association for the Advancement of Science ({AAAS})  

    DOI： 10.1126/sciadv.aay2042

    researchmap

▼display all

MISC

  • 特集 高速分子動画:動的構造からタンパク質分子制御へ Ⅵ.高速分子動画の実例:光作動性タンパク質 光活性化アデニル酸シクラーゼ合成酵素の活性化機構の解明

    石本 直偉士, 朴 三用

    生体の科学   75 ( 3 )   257 - 262   2024.6

    　More details

    Publisher：株式会社医学書院  

    DOI： 10.11477/mf.2425201863

    CiNii Research

    researchmap

Presentations

  • ケモカイン受容体CXCR1におけるインターロイキン8の選択的認識に関する構造生物学的研究

    石本直偉士

    生物無機化学シンポジウム2024  2024.1 

    　More details

    Event date： 2024.1 - 2024.2

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    researchmap

  • Structural basis of CXC chemokine receptor 1 ligand binding and activation.

    Naito Ishimoto, Jae-Hyun Park, Kouki Kawakami, Michiko Tajiri, Kenji Mizutani, Satoko Akashi, Jeremy R.H. Tame, Asuka Inoue, Sam-Yong Park

    生理研研究会2023「クライオ電子顕微鏡とその周辺」  2023.11 

    　More details

    Event date： 2023.11

    Language：English   Presentation type：Poster presentation  

    researchmap

  • 創薬・新規治療法の基盤となる対象タンパク質の構造生物学的研究

    石本直偉士

    未来の博士フェス2023  2023.9 

    　More details

    Event date： 2023.9

    Language：Japanese  

    File： mirainohakase2023_program.pdf

    researchmap

  • Structural basis of CXC chemokine receptor 1 ligand binding and activation.

    Naito Ishimoto, Jae-Hyun Park, Kouki Kawakami, Michiko Tajiri, Kenji Mizutani, Satoko Akashi, Jeremy R.H. Tame, Asuka Inoue, Sam-Yong Park

    令和5年度 新学術領域研究「高速分子動画」シンポジウム  2023.5 

    　More details

    Event date： 2023.5

    Language：English   Presentation type：Poster presentation  

    researchmap

  • Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface.

    Naito Ishimoto, Yunseok Heo, Ye-Eun Jeon, Ji-Hye Yun, Mio Ohki, Yuki Anraku, Mina Sasaki, Shunsuke Kita, Hideo Fukuhara, Tatsuya Ikuta, Koki Kawakami, Asuka Inoue, Katsumi Maenaka, Jeremy R.H. Tame, Weontae Lee, Sam-Yong Park

    令和5年度 新学術領域研究「高速分子動画」シンポジウム  2023.5 

    　More details

    Event date： 2023.5

    Language：English  

    researchmap

  • Reaction mechanism of photoactivated adenylate cyclase OaPAC studied by dynamic structural analysis

    Naito Ishimoto, Yasufumi Umena, Tramparia Sofia, Soichiro Tsujino, Takashi Tomizaki, Sam-Yong Park

    The Biophysical Society of Japan  2022.9 

    　More details

    Event date： 2022.9

    Language：English   Presentation type：Oral presentation (general)  

    researchmap

  • 海洋微生物塩化物イオンポンプロドプシンNM-R3の機構解明

    石本 直偉士, 水野 操, 川瀬 眞吾, 明石 知子, 竹田 一旗, Ji-Hye Yun, 村岡 貴博, 水谷 泰久, 朴 三用

    第44回 日本分子生物学会年会  2021.12 

    　More details

    Event date： 2021.12

    Language：Japanese   Presentation type：Poster presentation  

    researchmap

▼display all

Awards

  • YCU Best Student Award （旧学長賞）

    2024.3   横浜市立大学  

    石本直偉士

    　More details

  • 生理研研究会 2023「クライオ電子顕微鏡とその周辺」優秀ポスター賞

    2023.11   生理研研究会  

    石本直偉士

    　More details

  • 2022年度（令和4年度）奨学生

    2022.3   首藤奨学財団   ケモカイン受容体CXCR1におけるインターロイキン8の選択的認識に関する構造生物学的研究

    石本直偉士

    　More details

  • 2021年度（令和3年度）第32期奨学生

    2021.4   山田長満奨学会  

    石本直偉士

    　More details

Research Projects

  • インフルエンザウイルスNPタンパク質の核内輸送の機構解明

    Grant number：25K18415  2025.4 - 2027.3

    日本学術振興会  科学研究費助成事業  若手研究

    石本 直偉士

    　 More details

    Authorship：Principal investigator 

    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    researchmap

  • 脂肪酸受容体GPCRの立体構造の解明と機能解析

    2024.4 - 2025.3

    内藤記念科学振興財団  2023年度 内藤記念海外研究留学助成金 

    　 More details

    Authorship：Principal investigator 

    researchmap

  • 光活性化アデニル酸シクラーゼ蛋白分子の光遺伝学による細胞内での情報伝達分子の制御

    2021.4 - 2024.3

    サントリー生命医科学財団  SUNBOR SCHOLARSHIP 

    　 More details

    Authorship：Principal investigator 

    researchmap

  • 創薬・新規治療法の基盤となる対象タンパク質の構造生物学的研究

    2021.4 - 2024.3

    横浜市立大学  データ思考イノベーティブ人材フェローシップ 

    　 More details

    Authorship：Principal investigator 

    researchmap