Structural studies of HLA to develop of rational medicines for DIHS treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Teikyo University
• Principal Investigator: Kusakabe Yoshio 帝京大学, 薬学部, 講師 (30338537)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アレルギー / 重症型薬疹 / DIHS / 立体構造 / インシリコ

Outline of Final Research Achievements

In this study, we aimed to clarify the three-dimensional structure of HLA-B*13:01 by X-ray crystal structure analysis. Since HLA-B*13:01 forms a complex with β2-Microglobulin, it is necessary to obtain a complex of the two in order to perform crystal structure analysis. For each protein, expression systems with and without His tags were constructed, and expression and purification were performed, and we succeeded in obtaining proteins free of impurities. After that, we confirmed the formation of the complex by gel filtration chromatography, but we were unable to obtain a complex with or without a tag. Therefore, we predicted the complex between HLA-B*13:01 and β2-Microglobulin in silico, and found that a peptide of dipeptide or more is required for the complex to form.

Free Research Field

皮膚科

Academic Significance and Societal Importance of the Research Achievements

HLA-B*13:01のX線結晶構造解析を目指したが、β2-Microgloblinとの複合体を得ることが出来なかった。そこで、HLA-B*13:01とβ2-Microgloblinの複合体をin silicoで明らかにし、DIHSを引き起こすアロプリノールとフェノバルビタールをドッキングの手法で結合様式を予測した結果、共通の結合が見つけることが出来た。このことからHLA-B*13:01を持つ人に対して薬疹を引き起こす医薬品の共通構造を予測することが出来、この結果を応用することでHLA-B*13:01を持つ人が薬疹を引き起こす医薬品をあらかじめ予測することが出来ると考えられる。