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膜孔形成毒素の動的な作用機構の解明

Publicly Offered Research

Project AreaDynamical ordering of biomolecular systems for creation of integrated functions
Project/Area Number 26102501
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionHokkaido University

Principal Investigator

田中 良和  北海道大学, 先端生命科学研究科(研究院), 准教授 (20374225)

Project Period (FY) 2014-07-10 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords蛋白質 / 微生物 / X線
Outline of Annual Research Achievements

院内感染の原因菌として知られる黄色ブドウ球菌は,様々な膜孔形成毒素を分泌し,宿主の血球細胞を破壊する.αヘモリジン(αHL)は膜孔形成毒素の一つであり,βバレル型の膜孔を形成して赤血球を破壊する.αHLは可溶性の単量体として分泌されるが,赤血球の膜上で会合してpreporeと呼ばれる中間体構造を形成した後,大きく構造変化して膜孔を形成する.膜孔形成機構の理解に向け,様々な膜孔形成毒素において,各段階の結晶構造解析が行われてきたが,αHLは膜孔へと会合しやすく,これまで,膜孔の構造のみしか決定されていなかった.そこで本研究では,過去の報告をもとに,安定な単量体およびpreporeを形成する変異体を取得し(H35A変異体およびW179A/R200A二重変異体),これら結晶構造解析によりαHLの一連の動的な構造変化を明らかにした.また,結晶構造解析の結果,Asp45-Tyr118間の水素結合,およびN末端アミノラッチ領域が機能発現に重要な役割を担う事が明らかになったため,これらの部位の変異体蛋白質を調製し,その膜孔形成活性を評価した.これらの結果に基づき,αHLの動的な膜孔形成機構を解明した.得られた成果を,Toxicon誌に報告したほか,第15回日本蛋白質科学会年会,生理学研究所 研究会「膜システムの機能的・構造的統合」,The 3rd International Life-Science Symposium,Hokkaido University / Pusan National University Joint Symposium 2016 in Busan,2015年度量子ビームサイエンスフェスタ・第7回MLFシンポジウム・第33回PFシンポジウムにて発表した.

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (20 results)

All 2016 2015 2014 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Structural basis for pore-forming mechanism of staphylococcal α-hemolysin2015

    • Author(s)
      Takaki Sugawara, Daichi Yamashita, Koji Kato, Zhao Peng, Junki Ueda, Jun Kaneko, Yoshiyuki Kamio, Yoshikazu Tanaka, Min Yao
    • Journal Title

      Toxicon

      Volume: 108 Pages: 226-231

    • DOI

      10.1016/j.toxicon.2015.09.033

    • NAID

      120005898548

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution2015

    • Author(s)
      Zuoqi Gai, Asuka Matsuno, Koji Kato, Sanae Kato, Md Rafiqul Islam Khan, Takeshi Shimizu, Takeya Yoshioka, Yuki Kato, Hideki Kishimura, Gaku Kanno, Yoshikatsu Miyabe, Tohru Terada Yoshikazu Tanaka, and Min Yao
    • Journal Title

      Structure

      Volume: 23 Issue: 12 Pages: 2204-2212

    • DOI

      10.1016/j.str.2015.09.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 黄色ブドウ球菌が産生する膜孔形成毒素の作用機構2015

    • Author(s)
      田中良和
    • Journal Title

      Isotope News

      Volume: 736 Pages: 7-11

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 黄色ブドウ球菌の2成分性膜孔形成毒素γヘモリジンの膜孔形成メカニズム 失敗から明らかになった毒素の戦略2015

    • Author(s)
      田中良和
    • Journal Title

      化学と生物

      Volume: 53 Pages: 136-137

    • NAID

      130005126417

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18S rRNA2014

    • Author(s)
      Satoshi Ito, Sayuri Horikawa, Tateki Suzuki, Hiroki Kawauchi, Yoshikazu Tanaka, Takeo Suzuki, and Tsutomu Suzuki
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 289 Issue: 52 Pages: 35724-35730

    • DOI

      10.1074/jbc.c114.602698

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins2014

    • Author(s)
      Daichi Yamashita, Takaki Sugawara, Miyu Takeshita, Jun Kaneko, Yoshiyuki Kamio, Isao Tanaka, Yoshikazu Tanaka, and Min Yao
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 4897-4897

    • DOI

      10.1038/ncomms5897

    • NAID

      120005572422

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural and genomic DNA analysis of the putative TetR transcriptional repressor SCO7518 from Streptomyces coelicolor A3(2)2014

    • Author(s)
      Takeshi Hayashi, Yoshikazu Tanaka, Naoki Sakai, Ui Okada, Min Yao, Nobuhisa Watanabe, Tomohiro Tamura, and Isao Tanaka
    • Journal Title

      FEBS Letters

      Volume: 588 Issue: 23 Pages: 4311-4318

    • DOI

      10.1016/j.febslet.2014.09.037

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anchoring protein crystals to mounting loops with hydrogel using inkjet technology2014

    • Author(s)
      Akira Shinoda, Yoshikazu Tanaka, Min Yao and Isao Tanaka
    • Journal Title

      Acta Crystallographica Section D

      Volume: D70 Issue: 11 Pages: 2794-2799

    • DOI

      10.1107/s139900471401476x

    • NAID

      120005530838

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleoid compaction by MrgAAsp56Ala/Glu60Ala does not contribute to staphylococcal cell survival against oxidative stress and phagocytic killing by macrophage2014

    • Author(s)
      Yuri Ushijima, Ryosuke L. Ohniwa, Atsushi Maruyama, Shinji Saito, Yoshikazu Tanaka, and Kazuya Morikawa
    • Journal Title

      FEMS Microbiology Letters

      Volume: 360 Issue: 2 Pages: 144-151

    • DOI

      10.1111/1574-6968.12598

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray crystallographic analysis of a bacterial Asn-transamidosome2014

    • Author(s)
      Tateki Suzuki, Keitaro Yamashita, Yoshikazu Tanaka, Isao Tanaka, and Min Yao
    • Journal Title

      Acta Crystallographica Section F

      Volume: F70 Issue: 6 Pages: 790-793

    • DOI

      10.1107/s2053230x14007274

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 黄色ブドウ球菌由来α-hemolysinの分子機構の解明(Molecular mechanism of staphylococcal α-hemolysin)2016

    • Author(s)
      菅原宇希,山下大智,加藤公児,金子淳,神尾好是,田中良和,姚閔
    • Organizer
      2015年度量子ビームサイエンスフェスタ・第7回MLFシンポジウム・第33回PFシンポジウム
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Year and Date
      2016-03-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular mechanism of staphylococcal pore forming toxin2016

    • Author(s)
      Yoshikazu Tanaka
    • Organizer
      Hokkaido University / Pusan National University Joint Symposium 2016 in Busan
    • Place of Presentation
      釜山広域市(韓国)
    • Year and Date
      2016-03-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] X線結晶構造解析により明らかになった黄色ブドウ球菌の膜孔形成毒素蛋白質の膜孔形成機構2015

    • Author(s)
      田中良和
    • Organizer
      生理学研究所 研究会「膜システムの機能的・構造的統合」
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 黄色ブドウ球菌が赤血球を破壊する毒素の作用原理(Molecular mechanism of pore forming toxin from Staphylococcus aureus)2015

    • Author(s)
      田中良和,山下大智,菅原宇希,金子淳,神尾好是,姚閔
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 黄色ブドウ球菌由来α-ヘモリジンの膜孔形成機構(Pore formation mechanism of staphylococcal α-hemolysin)2015

    • Author(s)
      菅原宇希,山下大智,加藤公児,金子淳,神尾好是,田中良和,姚閔
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      あわぎんホール(徳島県徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 分子量4MDaの細胞外酸素運搬体ヘモシアニンの解離-再会合2014

    • Author(s)
      加藤早苗,Md. Rafiqul Islam Khan,吉岡武也,信太茂春,岸村栄毅,清水健志,田中良和
    • Organizer
      第87回 日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 黄色ブドウ球菌由来α-ヘモリジン単量体の結晶構造2014

    • Author(s)
      菅原宇希,山下大智,田中良和,金子淳,神尾好是,田中勲,姚閔
    • Organizer
      第52回 日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 結晶構造解析により明らかになった黄色ブドウ球菌由来膜孔形成毒素の分子機構2014

    • Author(s)
      田中良和,山下大智,菅原宇希,金子淳,神尾好是,田中勲,姚閔
    • Organizer
      第61回 トキシンシンポジウム
    • Place of Presentation
      ルネッサンスリゾートナルト(鳴門市)
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Book] Essential タンパク質科学 第2章2016

    • Author(s)
      田中良和
    • Total Pages
      36
    • Publisher
      南江堂
    • Related Report
      2015 Annual Research Report
  • [Remarks] 北海道大学 X線構造生物学研究室 ホームページ

    • URL

      http://altair.sci.hokudai.ac.jp/g6/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report

URL: 

Published: 2014-11-20   Modified: 2018-03-28  

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