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Substrate recognition mechanism of KSHV immune evasion molecule MIR

Research Project

Project/Area Number 15K08504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionShowa Pharmaceutical University

Principal Investigator

KAJIKAWA Mizuho  昭和薬科大学, 薬学部, 講師 (00464389)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsウイルス / 免疫回避 / 免疫受容体 / 膜タンパク質 / ユビキチンリガーゼ / ナノディスク / カポジ肉腫関連ヘルペスウイルス
Outline of Final Research Achievements

Kaposi’s sarcoma associated herpesvirus expresses immune evasion molecule family MIR, which is membrane-bound E3 ubiquitin ligases to downregulate several immune proteins on host cell surface. Our previous study revealed that MIR recognizes substrates through transmembrane and extracellular region. In this study, to reveal molecular basis of substrate recognition by MIR, recombinant MIR protein containing two transmembrane regions and extracellular region was prepared and reconstructed in nanodisc, which is artificial lipid bilayer. MIR-nanodisc was subjected to solution NMR analysis; however, HSQC signal was too low to determine structure of MIR. In order to improve molecular stability of MIR, we performed mutational analysis of MIR and revealed that cytoplasmic tail of MIR is essential to stabilize MIR structure.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2018 2016 2015

All Presentation (6 results)

  • [Presentation] カポジ肉腫関連ヘルペスウイルス免疫回避膜タンパク質MIR2の細胞質尾部は機能的発現に必須である2018

    • Author(s)
      梶川瑞穂、高橋勇人、楠陽輔、加藤功也、嶋秀明、井上能博、石戸聡
    • Organizer
      第28回日本生体防御学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MHC class II 恒常的ユビキチン化モデルマウスの解析2016

    • Author(s)
      小泉龍士、嶋秀明、梶川瑞穂、井上能博、石戸聡
    • Organizer
      第17回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      帝京大学板橋キャンパス(東京都 板橋区)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] ウイルスユビキチンリガーゼMIR2による免疫受容体膜貫通領域の新たな認識機構2015

    • Author(s)
      梶川瑞穂、加藤功也、木村美奈子、嶋秀明、井上能博、石戸聡
    • Organizer
      BMB2015(第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] KSHVユビキチンリガーゼMIRによる膜貫通へリックス間相互作用を介した免疫受容体認識の分子基盤2015

    • Author(s)
      藏本彩、梶川瑞穂、木村美奈子、嶋秀明、井上能博、石戸聡
    • Organizer
      BMB2015(第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] KSHV免疫回避分子MIR2の膜貫通領域間ループはCD86膜貫通領域を認識する2015

    • Author(s)
      梶川瑞穂、加藤功也、木村美奈子、嶋秀明、井上能博、石戸聡
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Recognition mode of viral MIR E3 ubiquitin ligase-mediated targeting2015

    • Author(s)
      Satoshi Ishido, Mizuho Kajikawa, Pai-Chi Li, Yuji Sugita
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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