Structural analysis of HLA class I/II molecules

2014 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

構造生物化学