Structural basis of the co-stimulation receptors, CD28 family, and signalling molecules for drug discovery

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K14395
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38030:Applied biochemistry-related
• Research Institution: Hokkaido University (2023); High Energy Accelerator Research Organization (2022); Japan Synchrotron Radiation Research Institute (2018-2019)
• Principal Investigator: Inaba-Inoue Satomi 北海道大学, 先端生命科学研究院, 助教 (70785493)
• Project Period (FY): 2021-11-01 – 2024-03-31
• Keywords: 免疫系シグナル伝達 / 分子間相互作用 / X線小角散乱 / 複合体構造

Outline of Final Research Achievements

The purpose of this project is to focus on the signalling molecules involved in the activation of T cells in the acquired immunity mechanism and to elucidate the molecular recognition mechanisms to the intracellular regions of the receptors from multiple techniques. Structural characterisation of the intracellular regions of the co-stimulatory receptor CD28 and its family molecules in complex with the SH2 domains of adaptor proteins that bind to them, using X-ray crystallography, small-angle X-ray scattering and synchrotron radiation circular dichroism. These results provide more detailed structural information underlying molecular recognition.

Free Research Field

生物物理学・タンパク質科学・構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、獲得免疫におけるT細胞活性化初期シグナルに着目して、分子レベルでの知見を得ることができた。これらの詳細な分子間相互作用の情報は、今後創薬などの応用面において重要となってくると考えられる。また、複数の解析手法を組み合わせることで、特定の複合体を多面的な視点から明らかにし、その手法の有効性も示すことができた。今後、本研究対象のみならずタンパク質科学分野での幅広い利用が期待できる。