Structural study on the NKRP1A-LLT1 complex involved in the immune regulatory

• Project/Area Number: 16K18499
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: TADOKORO Takashi 北海道大学, 薬学研究院, 特任助教 (10762396)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免役受容体 / 相互作用 / 構造解析 / 表面プラズモン共鳴 / NKRP1A / 免疫受容体 / 結晶構造解析 / 蛋白質

Outline of Final Research Achievements

Human NKRP1A is an immunoreceptor that highly expressed in NK cells and Th17 cells, and is a member of the immunity checkpoint receptor which is attractive for a cancer drug discovery target in recent years. In this study, we aimed to clarify the interaction between NKRP1A and its ligand, LLT1, by physicochemical and structural biology and to elucidate the molecular basis of immune regulatory mechanism involving NKRP1A. An extensive mutagenesis at the interaction surface inferred from the NKRP1A-LLT1 complex model and binding analysis was carried out. The results suggested that the interaction might be precisely regulated to the extent that even a slight difference in amino acid side chain structure at the interacting surface is unacceptable.

Research Products

• [Journal Article] A trimeric structural fusion of an antagonistic tumor necrosis factor-α mutant enhances molecular stability and enables facile modification (2017)
  • Author(s): Masaki Inoue, Daisuke Ando, Haruhiko Kamada, Shintaro Taki, Mayumi Niiyama, Yohei Mukai, Takashi Tadokoro, Katsumi Maenaka, Taisuke Nakayama, Yuji Kado, Tsuyoshi Inoue, Yasuo Tsutsumi and Shin-ichi Tsunoda
  • Journal Title: J. Biol. Chem., Volume: in press Issue: 16 Pages: 235-237
  • DOI: 10.1074/jbc.m117.779686
  • Peer Reviewed / Open Access
• [Presentation] ヒト免疫受容体NKRP1AによるリガンドLLT1の分子認識機構 (2017)
  • Author(s): 田所高志、喜多俊介、松原永季、笠井宣征、玉置貴晴、岡部由紀、日下裕規、石山夢美、福原秀雄、上敷領淳、尾瀬農之、黒木喜美子、前仲勝実
  • Organizer: ConBio2017 生命科学系学会合同年次大会
• [Presentation] トラスツズマブ一本鎖Fv抗体断片の構築および高機能化 (2017)
  • Author(s): 田所高志、中村光太、坪井晴美、前田龍、松田彰、尾瀬農之、前仲勝実
  • Organizer: 日本蛋白質科学会年会
• [Presentation] 新規バイオ融合医薬品開発を目的としたHLAの蛍光修飾 (2017)
  • Author(s): 田所高志、可野巧、市川聡、松田彰、黒木 喜美子、前仲 勝実
  • Organizer: 日本ケミカルバイオロジー学会