Novel mechanism of glycan-mediated activation of cytokine receptors by lectins from marine sponges

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20589
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0603:Forestry and forest products science, applied aquatic science, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Watari Hiromi 北海道大学, 水産科学研究院, 助教 (30962758)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: トロンボポエチン受容体 / レクチン / 糖鎖 / 海洋天然物

Outline of Final Research Achievements

In our previous study, we clarified the mechanism of TPO receptor activation by thrombocorticin (ThC), a novel lectin derived from a marine sponge. We have expressed here recombinant proteins of various ThC mutants to reveal the details of TPO receptor activation by lectins via glycan. It was showed that wild-type ThC exhibited by far the strongest activity, but the three-dimensional structure of the expressed lectin was almost identical to ThC using a protein three-dimensional structure prediction tool, so the definitive reason that could explain the difference in activity has not been clarified. Further investigation is required, such as structural comparison of the complex with the TPO receptor.

Free Research Field

海洋天然物化学

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍という疾患においてThCによるTPO受容体活性化と同様の機構の存在が示唆されていたが、その詳細は不明であった。ThCによる活性化機構の解明により、TPO受容体上の糖鎖を介した活性化が、疾患の原因として実際に体内で生じていることを間接的ではあるものの、示した。本研究においてThCに類似した構造を持つレクチンがTPO受容体にどのような活性を示すかを調べることは、レクチンがTPO受容体の活性化をどのように調節しているのか、その疑問に対し新たな知見を与え、延いては未だ明らかとなっていない疾患の詳細の理解につながる。