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Development of Functional Protein Nanobuilding Block Complexes and their Applications

Research Project

Project/Area Number 19H02522
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionShinshu University

Principal Investigator

ARAI Ryoichi  信州大学, 学術研究院繊維学系, 准教授 (50344023)

Co-Investigator(Kenkyū-buntansha) 川上 了史  慶應義塾大学, 理工学部(矢上), 講師 (60566800)
宮田 健  鹿児島大学, 農水産獣医学域農学系, 准教授 (20448591)
迫野 昌文  富山大学, 学術研究部工学系, 准教授 (50391959)
舘野 浩章  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (30450670)
浅野 竜太郎  東京農工大学, 工学(系)研究科(研究院), 教授 (80323103)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordsタンパク質ナノブロック / 人工タンパク質デザイン / タンパク質複合体 / 立体構造解析 / 自己組織化 / タンパク質修飾 / 融合タンパク質 / レクチンナノブロック / タンパク質工学 / 構造機能解析 / タンパク質連結修飾
Outline of Research at the Start

これまでの人工タンパク質ナノブロック開発によって、多様なナノ構造複合体を創出してきたが、応用展開は今後の課題であった。そこで本研究では、機能性タンパク質ナノブロック複合体創製の基盤的プロセス技術開発と応用展開を目的とする。まず、①タンパク質ナノブロック複合体の立体構造解析、②新型タンパク質ナノブロックの設計開発、③多機能性修飾等により、多価多機能性タンパク質ナノブロック複合体創製の基盤的なプロセス技術を開発する。さらに、④レクチンナノブロックの創製や⑤タンパク質ナノブロック複合体ワクチンの開発により、生体分子工学等の学術的基盤となる成果のみならず、社会への波及効果の高い応用展開が期待できる。

Outline of Final Research Achievements

Aiming to functionalize to artificial protein nanoblocks and develop their application, we conducted research to develop fundamental process technology to create functional protein nanoblock complexes. First, the three-dimensional structure of the artificial protein nanoparticle complex TIP60 was solved using cryo-electron microscopy. We also succeeded in designing and developing mTIP60 (metal ion induced complex) and lectin nanoblock complexes fused with lectins (glycan-binding proteins). Furthermore, we conjugated functional domains to protein nanoblocks by using peptidyltransferase Sortase A and/or SpyTag/SpyCatcher system.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発したレクチンナノブロック複合体は、今後、糖鎖のかかわる生命現象を解明するための有用なツールとなるばかりでなく、癌や炎症などに伴う糖鎖変化や各種病気の診断、さらには糖鎖標的薬開発等に向けた応用展開も期待される。また、金属イオンにより形成が誘導される人工タンパク質ナノ粒子は、内部にDNAや低分子などを取り込むことが可能であり、ナノバイオカプセルやドラッグデリバリーシステム等への応用が期待される。以上のように、機能性タンパク質ナノブロック複合体を設計創製する基盤的プロセス技術の開発により、タンパク質工学分野等の学術的意義のみならず、将来的に波及効果の高い社会的意義を持つ成果が得られた。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (58 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 5 results) Presentation (35 results) (of which Int'l Joint Research: 9 results,  Invited: 4 results) Book (1 results) Remarks (6 results)

  • [Int'l Joint Research] Princeton University/University of Washington(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Princeton University/University of Washington(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Princeton University/University of Washington(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Reversible Assembly of an Artificial Protein Nanocage Using Alkaline Earth Metal Ions2023

    • Author(s)
      Ohara Naoya、Kawakami Norifumi、Arai Ryoichi、Adachi Naruhiko、Moriya Toshio、Kawasaki Masato、Miyamoto Kenji
    • Journal Title

      Journal of the American Chemical Society

      Volume: 145 Issue: 1 Pages: 216-223

    • DOI

      10.1021/jacs.2c09537

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] One-pot synthesis of fibrillar-shaped functional nanomaterial using microbial transglutaminase2023

    • Author(s)
      Sakono Masafumi、Nakamura Mitsuki、Ohshima Tatsuki、Miyakoshi Ayano、Arai Ryoichi、Minamihata Kosuke、Kamiya Noriho
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: - Issue: 6 Pages: 440-446

    • DOI

      10.1016/j.jbiosc.2023.03.015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enzymatic fabrication of multifunctional amyloid-based protein assembly2023

    • Author(s)
      Mitsuki Nakamura, Ryoichi Arai, Noriho Kamiya, Masafumi Sakono
    • Journal Title

      Chemistry Letters

      Volume: - Issue: 7 Pages: 538-541

    • DOI

      10.1246/cl.230156

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-Assembling Lectin Nano-Block Oligomers Enhance Binding Avidity to Glycans2022

    • Author(s)
      Irumagawa Shin、Hiemori Keiko、Saito Sayoko、Tateno Hiroaki、Arai Ryoichi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 2 Pages: 676-676

    • DOI

      10.3390/ijms23020676

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of pentaglycine-fused proteins using Escherichia coli expression system without in vitro peptidase treatment2022

    • Author(s)
      Sakono Masafumi、Oshima Tatsuki、Iwakawa Takako、Arai Ryoichi
    • Journal Title

      Protein Expression and Purification

      Volume: 194 Pages: 106068-106068

    • DOI

      10.1016/j.pep.2022.106068

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rational thermostabilisation of four-helix bundle dimeric de novo proteins2021

    • Author(s)
      Irumagawa Shin、Kobayashi Kaito、Saito Yutaka、Miyata Takeshi、Umetsu Mitsuo、Kameda Tomoshi、Arai Ryoichi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 7526-7526

    • DOI

      10.1038/s41598-021-86952-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Icosahedral 60-meric porous structure of designed supramolecular protein nanoparticle TIP602021

    • Author(s)
      Junya Obata, Norifumi Kawakami, Akihisa Tsutsumi, Erika Nasu, Kenji Miyamoto, Masahide Kikkawa, Ryoichi Arai
    • Journal Title

      Chemical Communications

      Volume: 79 Issue: 79 Pages: 10226-10229

    • DOI

      10.1039/d1cc03114g

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design of helical linkers for fusion proteins and protein-based nanostructures2021

    • Author(s)
      Ryoichi Arai
    • Journal Title

      Methods in Enzymology

      Volume: 647 Pages: 209-230

    • DOI

      10.1016/bs.mie.2020.10.003

    • ISBN
      9780128208182
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Nanopore-Controlled Dual-Surface Modifications on Artificial Protein Nanocages as Nanocarriers2021

    • Author(s)
      Nasu Erika、Kawakami Norifumi、Miyamoto Kenji
    • Journal Title

      ACS Applied Nano Materials

      Volume: 4 Issue: 3 Pages: 2434-2439

    • DOI

      10.1021/acsanm.0c02972

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and homogeneous electrochemical detection by fabricating a high affinity bispecific antibody-enzyme complex using two Catcher/Tag systems2021

    • Author(s)
      Kimura Hayato、Miura Daimei、Tsugawa Wakako、Ikebukuro Kazunori、Sode Koji、Asano Ryutaro
    • Journal Title

      Biosensors and Bioelectronics

      Volume: 175 Pages: 112885-112885

    • DOI

      10.1016/j.bios.2020.112885

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hyperstable De Novo Protein with a Dimeric Bisecting Topology2020

    • Author(s)
      Kimura Naoya、Mochizuki Kenji、Umezawa Koji、Hecht Michael H.、Arai Ryoichi
    • Journal Title

      ACS Synthetic Biology

      Volume: 9 Issue: 2 Pages: 254-259

    • DOI

      10.1021/acssynbio.9b00501

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Design of artificial protein complexes of protein nano-building blocks2019

    • Author(s)
      小林 直也、川上 了史、新井 亮一
    • Journal Title

      生化学

      Volume: 91 Issue: 2 Pages: 255-259

    • DOI

      10.14952/SEIKAGAKU.2019.910255

    • NAID

      40021942521

    • ISSN
      0037-1017
    • Year and Date
      2019-04-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 蛋白質ナノブロックによるレクチン超分子複合体の創出戦略2019

    • Author(s)
      入間川 伸,新井 亮一
    • Journal Title

      医学のあゆみ

      Volume: 269 Pages: 690-696

    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規人工酵素Syn-F4エンテロバクチンエステラーゼのX線結晶構造解析2022

    • Author(s)
      栗原航大, 梅澤公二, Ann E. Donnelly, Michael H. Hecht, 新井亮一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] イソペプチド結合タグを用いた多価抗体タンパク質ナノブロック複合体の開発2022

    • Author(s)
      髙橋五月, 浅野竜太郎, 山本雷蔵, 迫野昌文, 新井亮一
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 多価レクチンナノブロックWA20-ACG複合体の開発2021

    • Author(s)
      入間川 伸,舘野 浩章,新井 亮一
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 三量体レクチンを用いた蛋白質ナノブロックの自己組織化超分子複合体の創製2021

    • Author(s)
      貝川 はるか,舘野 浩章,新井 亮一
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Barium ion responsive reversible assembly of protein supramolecule TIP602021

    • Author(s)
      大原 直也,川上 了史,新井 亮一,宮本 憲二
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 蛋白質ナノブロックによる機能性人工蛋白質複合体の創製に向けて2021

    • Author(s)
      新井 亮一
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Icosahedral 60-meric porous structure of designed protein nanoparticle TIP602021

    • Author(s)
      Ryoichi Arai, Norifumi Kawakami, Junya Obata, Akihisa Tsutsumi, Kenji Miyamoto, Masahide Kikkawa
    • Organizer
      The Protein Society, the 36th Annual Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Self-assembling lectin nano-building blocks enhance avidity to glycans through polyvalent effect2021

    • Author(s)
      Shin Irumagawa, Hiroaki Tateno, Ryoichi Arai
    • Organizer
      The Protein Society, the 36th Annual Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Self-assembling functional complexes of protein nanobuilding blocks with a trimeric lectin2021

    • Author(s)
      Haruka Kaigawa, Hiroaki Tateno, Ryoichi Arai
    • Organizer
      The Protein Society, the 36th Annual Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Icosahedral 60-meric porous structure of designed supramolecular protein nanoparticle TIP602021

    • Author(s)
      Junya Obata, Norifumi Kawakami, Akihisa Tsutsumi, Erika Nasu, Kenji Miyamoto, Masahide Kikkawa, Ryoichi Arai
    • Organizer
      PDB 50th Anniversary Symposium in Asia
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中空タンパク質ナノ粒子TIP60への疎水性光増感剤の内包2021

    • Author(s)
      山下 舞佳、川上 了史、宮本 憲二
    • Organizer
      日本化学会 第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 人工タンパク質ナノ粒子TIP60の金属イオン応答性可逆的アセンブル手法の構築2021

    • Author(s)
      大原 直也、川上 了史、新井 亮一、宮本 憲二
    • Organizer
      日本化学会 第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 人工タンパク質ナノ粒子TIP60の表面孔の分子ふるい効果を利用した内外表面の機能化2021

    • Author(s)
      那須 英里圭、川上 了史、宮本 憲二
    • Organizer
      日本化学会 第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Structural Basis for Quenchbody (Q-body): Crystal Structures of the Fab Fragment of Anti-osteocalcin Antibody KTM2192020

    • Author(s)
      Shuma Yazaki, Misaki Komatsu, Jinhua Dong, Hiroshi Ueda, Ryoichi Arai
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Rational Stabilization of Dimeric Four-Helix Bundle De Novo Proteins Using Molecular Dynamics Simulation2020

    • Author(s)
      Shin Irumagawa, Kaito Kobayashi, Yutaka Saito, Takeshi Miyata, Mitsuo Umetsu, Tomoshi Kameda, Ryoichi Arai
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Incorporation of Hydrophobic Small Molecules in the Artificial Protein Nanoparticle TIP602020

    • Author(s)
      Norifumi Kawakami, Maika Yamashita, Kenji Miyamoto
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Metal Inducive Assembly of a Newly Designed Protein Cage TIP602020

    • Author(s)
      Naoya Ohara, Norifumi Kawakami, Kenji Miyamoto
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Dual-Surface Functionalization of an Artificial Protein Nanocapsule Based on Molecular Sieving Effect of its Porous Surface2020

    • Author(s)
      Erika Nasu, Norifumi Kawakami, Kenji Miyamoto
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Development of highly sensitive anti-human hemoglobin sensing elements using a universal fabrication technology for antibody-enzyme complex2020

    • Author(s)
      Daimei Miura, Hayato Kimura, Wakako Tsugawa, Kazunori Ikebukuro, Koji Sode, Ryutaro Asano
    • Organizer
      第20回日本蛋白質科学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 分子標的蛍光インジケーターとグルタチオンS-トランスフェラーゼ複合体のX結晶構造解析2020

    • Author(s)
      矢崎 崇真, 岡島 崇文, 瀧 真清, 新井 亮一
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規人工酵素Syn-F4エンテロバクチンエステラーゼのX線結晶構造解析2020

    • Author(s)
      栗原 航大, 梅澤 公二, Sha Tao, Ann E Donnelly, Michael H Hecht, 新井 亮一
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] グルコース脱水素酵素のスプリット化と電気化学センサー応用に向けた検討2020

    • Author(s)
      飛田 悠花、木村 勇人、津川 若子、池袋 一典、早出 広司、浅野 竜太郎
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 自己組織化レクチンナノブロックWA20-ACG複合体の開発2020

    • Author(s)
      入間川 伸、 舘野 浩章、新井 亮一
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 人工蛋白質ナノ粒子TIP60の正20面体型60量体多孔質構造2020

    • Author(s)
      小幡 隼也、川上 了史、包 明久、宮本 憲二、吉川 雅英、新井 亮一
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 三量体レクチンを用いたレクチンナノブロックの自己組織化タンパク質超分子複合体の創製2020

    • Author(s)
      貝川 はるか、舘野 浩章、新井 亮一
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 形から入るタンパク質ナノ粒子の設計と機能化2020

    • Author(s)
      川上 了史
    • Organizer
      SICE分子ロボティクス研究会 第1回オンライン定例研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 中空タンパク質ナノ粒子TIP60の内部疎水化と疎水性小分子の内包2020

    • Author(s)
      山下 舞佳、川上 了史、宮本 憲二
    • Organizer
      第22回生体触媒化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 切頂二十面体型人工タンパク質ナノ粒子TIP60のクライオ電子顕微鏡解析2019

    • Author(s)
      小幡 隼也、川上 了史、包 明久、宮本 憲二、吉川 雅英、新井 亮一
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規人工酵素Syn-F4エンテロバクチンエステラーゼのX線結晶構造解析2019

    • Author(s)
      栗原 航大、Michael H. Hecht、新井 亮一
    • Organizer
      第19回日本蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Thermal Reconstruction of Protein Nanobuilding Block Complexes Using an Ultra-Stable de Novo Protein Domain2019

    • Author(s)
      Naoya Kimura, Naoya Kobayashi, Michael H. Hecht, Ryoichi Arai
    • Organizer
      Gordon Research Conference, Proteins
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Thermal Reconstruction of Protein Nano-building Block Complexes Using an Ultra-Stable de Novo Protein Domain2019

    • Author(s)
      Naoya Kimura, Naoya Kobayashi, Ryoichi Arai
    • Organizer
      The Protein Society, 33rd Annual Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Thermal Reconstruction of Protein Nanobuilding Block Complexes Using an Ultra-Stable de Novo Protein Domain2019

    • Author(s)
      Naoya Kimura, Naoya Kobayashi, Michael H. Hecht, Ryoichi Arai
    • Organizer
      RosettaCON 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Thermal Reconstruction of Protein Nanobuilding Block Complexes Using an Ultra-Stable de Novo Protein Domain2019

    • Author(s)
      Naoya Kimura, Naoya Kobayashi, Michael H. Hecht, Ryoichi Arai
    • Organizer
      Innovations in Imaging for the Life Sciences
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] タンパク質ナノブロックによる自己組織化ナノ構造複合体の創製2019

    • Author(s)
      新井 亮一
    • Organizer
      第26回ペプチドフォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Self-Assembling Supramolecular Nanostructures Constructed from Protein Nano-Building Blocks2019

    • Author(s)
      Ryoichi Arai
    • Organizer
      IPNF 2019 (International Powder and Nanotechnology Forum)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] クライオ電子顕微鏡ハンドブック(第4章第6節 人工設計タンパク質ナノ粒子TIP60の立体構造解析)2023

    • Author(s)
      新井亮一,川上了史,小幡隼也,包明久,那須英里圭,宮本憲二,吉川雅英(難波 啓一、加藤 貴之、牧野 文信 監修)
    • Total Pages
      10
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860438043
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    • URL

      http://fiber.shinshu-u.ac.jp/arai/index.html

    • Related Report
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    • URL

      http://soar-rd.shinshu-u.ac.jp/profile/ja.OVkUjFkV.html

    • Related Report
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    • URL

      http://www.shinshu-u.ac.jp/faculty/textiles//news/2020/02/140471.html

    • Related Report
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    • URL

      https://www.shinshu-u.ac.jp/institution/ibs/topics/cat15431/post-35.html

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    • URL

      https://eurekalert.org/pub_releases/2020-02/su-sah022820.php

    • Related Report
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  • [Remarks] 新井亮一研究室ホームページ

    • URL

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Published: 2019-04-18   Modified: 2024-01-30  

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