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Structural elucidation of a risk factor for Alzheimer's Disease, sorLA extracellular region

Research Project

Project/Area Number 26840022
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Structural biochemistry
Research InstitutionOsaka University

Principal Investigator

Kitago Yu  大阪大学, たんぱく質研究所, 助教 (60507185)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアルツハイマー病 / sorLA / 細胞外蛋白質 / 結晶化 / 電子顕微鏡 / 培養細胞 / Vps10p / 細胞外 / 動物細胞 / 細胞外領域 / ネガティブ染色
Outline of Final Research Achievements

In this research project, I have tried to reveal the entire extracellular region of sorLA (sorLAect: 2040 amino acids). SorLA is a single-pass transmembrane protein and is recognized as the potent risk factor of Alzheimer’s disease. At the beginning, it was technically impossible to obtain the recombinant sorLAect, and so I planed the structural study using the several divided portions of sorLAect. However, at the early stage of this project, I found the novel way to express the sorLAect by the co-expression method with a chaperon protein. Then I changed the plan for this project to establishing the expression and purification system of sorLAect for the single-molecule visualization using electron microscope. As a result, I successfully obtained the first negatively stained electron micrographs of sorLAect in the world, which showed that sorLAect takes an extended conformation without any sharp turns.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (6 results)

All 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (2 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Weill Cornell Medical College/Petsko Laboratory(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 巨大受容体sorLAのVps10pドメインによるアミロイドペプチド認>識の分子機構2015

    • Author(s)
      北郷 悠
    • Journal Title

      日本結晶学会誌

      Volume: 57 Pages: 331-337

    • Related Report
      2015 Research-status Report
  • [Journal Article] 巨大受容体sorLAのVps10pドメインによるアミロイドβ認識機構とそのAlzheimer病発症における役割2015

    • Author(s)
      北郷 悠,高木 淳一
    • Journal Title

      医学のあゆみ

      Volume: 254 Pages: 535-539

    • Related Report
      2015 Research-status Report
  • [Presentation] New format antibody drives the crystallization of sorLA Vps10p domain2016

    • Author(s)
      Kitago Y, Arimori T, Takagi J.
    • Organizer
      Diffraction Methods in Structural Biology, Gordon Research Conference
    • Place of Presentation
      Bates College, Lewiston ME, USA
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特異抗体FabによるSorLA Vps10pドメインの結晶化促進2016

    • Author(s)
      北郷 悠,高木 淳一
    • Organizer
      第16回日本蛋白質科学会年会
    • Place of Presentation
      福岡国際会議場(福岡県,福岡市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Molecular mechanism for peptide recognition by sorLA Vps10p domain2015

    • Author(s)
      Yu Kitago
    • Organizer
      The 10th International Symposium of the Institute Network
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2022-02-16  

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