Structural biology study on the interactions between lectins and branched glycans

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04758
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Tohoku Medical and Pharmaceutical University (2018-2019); Institute of Physical and Chemical Research (2016-2017)
• Principal Investigator: Yamaguchi Yoshiki 東北医科薬科大学, 薬学部, 教授 (90323451)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 糖鎖 / レクチン / X線結晶構造解析 / NMR / 分子動力学 / ダイナミクス

Outline of Final Research Achievements

Branched glycans attached to proteins play many diverse roles in protein quality control and cell-cell communication etc. Many of the glycan functions are attained through interactions with lectin receptors. However, we still do not know much about the 3D structure and interaction in detail. In this study, we aimed to understand the role of each glycan branch in interacting with lectin receptors. To attain this, we used “branched” glycan unit, not “linear” oligosaccharide as lectin ligands. Here we revealed that lectin receptors are categorized into two types, one binds to both branches irrespective of the branch position, and the other selectively binds to one of the glycan branches.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

糖鎖の分岐構造の生物学的意義については、その多価性によるレクチン受容体とのみかけの親和性の増大が従来報告されてきた。しかしながら、分岐構造の性質や生物学的役割の違についての理解はあまり進んでいなかった。本研究の遂行により、レクチン受容体との相互作用における分岐糖鎖の各分枝の役割の一旦を構造生物学的に解明することに成功した。得られた知見は、生理活性を示す糖鎖誘導体の開発（ワクチン、アジュバント）やレクチン受容体をターゲットとした創薬研究への貢献につながる。