Structural analysis of HLA class I/II molecules

• Project Area: HLA 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 Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The 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: ¥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)
• Keywords: HLA / 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

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.

Research Products

• [Journal Article] Structural basis for the specific recognition of the major antigenic peptide from the Japanese ceder 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 Pages: 3016-3027
  • DOI: 10.1016/j.jmb.2014.06.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Cedar pollen peptide・HLA-DP5 complex forms a homophilic assembly for T cell activation (2014)
  • 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
  • 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