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Structural analysis of HLA class I/II molecules

Planned Research

Project AreaHLA polymorphism, disease and evolution
Project/Area Number 22133004
Research Category

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

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

YOKOYAMA Shigeyuki  独立行政法人理化学研究所, 横山構造生物学研究室, 上席研究員 (00159229)

Co-Investigator(Kenkyū-buntansha) SHIROUZU Mikako  独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, 副センター長 (70280732)
HONMA Teruki  独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, チームリーダー (10466039)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥161,070,000 (Direct Cost: ¥123,900,000、Indirect Cost: ¥37,170,000)
Fiscal Year 2014: ¥39,780,000 (Direct Cost: ¥30,600,000、Indirect Cost: ¥9,180,000)
Fiscal Year 2013: ¥41,080,000 (Direct Cost: ¥31,600,000、Indirect Cost: ¥9,480,000)
Fiscal Year 2012: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2011: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
Fiscal Year 2010: ¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000)
KeywordsHLA / ペプチド / 立体構造 / タンパク質 / 免疫学 / 医薬品設計 / X線結晶構造解析 / 構造生物学 / 蛋白質 / 分子認識
Outline of Final Research Achievements

In this project, we performed the protein expression, purification, and crystallization of HLA molecules, HLA-DP5, HLA-DR53, and HLA-DR4, bound to their antigenic peptide. Thereby, we successfully determined the crystal structure of HLA-DP5 in complex with Cryptomeria japonica 1 peptide (pCry j 1), derived from Japanese cedar pollen. Based on this structural information, we designed ten compounds to inhibit pCry j 1 binding to HLA-DP5, as evaluation test candidates for the peptide-binding affinity. Furthermore, we determined the crystal structure of HLA-DP5 in complex with pCry j 1, including the flanking region.

Report

(2 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (3 results)

All 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Structural Basis for the Specific Recognition of the Major Antigenic Peptide from the Japanese Cedar Pollen Allergen Cry j 1 by HLA-DP5.2014

    • Author(s)
      Kusano S, Kukimoto-Niino M, Satta Y, Ohsawa N, Uchikubo-Kamo T, Wakiyama M, Ikeda M, Terada T, Yamamoto K, Nishimura Y, Shirouzu M, Sasazuki T, Yokoyama S.
    • Journal Title

      J Mol Biol.

      Volume: 426 Issue: 17 Pages: 3016-3027

    • DOI

      10.1016/j.jmb.2014.06.020

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Cedar pollen peptide・HLA-DP5 complex forms a homophilic assembly for T cell activation2014

    • Author(s)
      草野清輔、横山茂之、笹月健彦
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2014-12-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] HLA-DP5によるスギ花粉抗原Cry j 1の特異的認識に対する構造的基盤2014

    • Author(s)
      草野清輔、新野睦子、颯田葉子、大沢登、加茂友美、脇山素明、池田眞理子、寺田貴帆、山本健、西村泰治、白水美香子、笹月健彦、横山茂之
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report

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Published: 2010-08-23   Modified: 2023-03-23  

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