2023 Fiscal Year Final Research Report

Mechanism for diversifying the branched structure of GPI elucidated by interdisciplinary research in glycochemistry and glycobiology

Research Project

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Project/Area Number	21K05401
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 38040:Bioorganic chemistry-related
Research Institution	Gifu University
Principal Investigator	Tanaka Hide-Nori 岐阜大学, 糖鎖生命コア研究所, 助教 (20725064)
Co-Investigator(Kenkyū-buntansha)	藤田盛久岐阜大学, 糖鎖生命コア研究所, 教授 (30532056) 平田哲也岐阜大学, 高等研究院, 特任助教 (90780651)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	糖脂質GPI / 糖鎖合成 / 蛍光プローブ / 糖転移酵素 / B3GALT4 / PGAP4
Outline of Final Research Achievements	GPI is a glycolipid that is widely conserved among eukaryotes. It has a common core structure among eukaryotes, and mammalian GPI has a side chain with GlcNAc, followed by Gal, and Sia. It is also known that the side chain structure varies depending on the type of protein. In recent years, it has been revealed that the Gal transferase that works in GPI side chain elongation is the sphingoglycolipid GM1 synthase B3GALT4. In this study, we aimed to elucidate the mechanism of diversification of GPI side chain structure by interdisciplinary research in glycochemistry and glycobiology. To clarify the enzymatic properties of B3GALT4, we aimed to chemically synthesize GPI-GalNAc, which serves as the enzyme substrate, and worked on the synthesis of each unit.
Free Research Field	生物有機化学
Academic Significance and Societal Importance of the Research Achievements	糖脂質GPIは細胞内で小胞体とゴルジ体に存在する19の酵素群によって生合成されるが、これら生合成酵素の酵素学的性質は未だに何一つとして解析されていない。GPI生合成メカニズム解析が進んでいない原因として挙げられるのが、in vitro酵素活性評価系の構築の難しさである。特に酵素活性評価に必要とされる量の高純度GPI分子を天然から入手できないことが大きな障壁となっていた。本研究では、酵素基質であるGPI分子を高純度かつ大量に供給できる合成基盤を確立することでこの難題を解決し、GPI生合成酵素の酵素学的性質を世界で明らかにする点で学術的意義が高い。